Endovascular navigation system and method

ABSTRACT

An endovascular navigation and positioning system including a transducer on a distal end of an endovascular instrument, a control system connected to the transducer, the control system being configured to generate and receive at least one acoustic signal using the transducer, a pre-processor containing computer-readable instructions for manipulating the acoustic signal input to extract information related to desired parameters, a processor configured to evaluate the parameters to generate an output related to guidance of the instrument, and an output device for displaying an indication of the output generated by the processor. The processor may evaluate the information using artificial intelligence including inference rules related to navigation state, comparisons to information in a database, and probabilities, among others. The system may use an electrical signal as a confirmation input. Further disclosed is a method of navigating and positioning an endovascular device in a vasculature.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 61/411,412 filed Nov. 8, 2010, entitled“Endovascular Navigation System and Method,” by Wenkang Qi and BradHill, the entirety of which is incorporated herein by reference for allpurposes.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

FIELD OF THE INVENTION

This invention relates, in general, to an endovascular navigation systemand methods for guiding and positioning an endovascular device using analgorithm-based pattern recognition processor.

BACKGROUND OF THE INVENTION

This invention provides a method to substantially increase the accuracyand reduce the need for imaging related to placing an intravascularcatheter or other device. Aspects of the invention relate to theguidance, positioning and placement confirmation of intravasculardevices, such as catheters, stylets, guidewires and other elongatebodies that are typically inserted percutaneously into the venous orarterial vasculature, including flexible elongate bodies. Currently,these goals are suboptimally achieved using x-ray imaging, fluoroscopy,and in some cases ultrasound imaging. ECG alone is used but has severelimitations with accuracy, navigation along the entire venous pathway,and is of minimal value in the presence of arrhythmia or abnormal heartcardiac activity. Reduced imaging reduces the amount of radiation thatpatients are subjected to, reduces the time required for the procedure,and decreases the cost of the procedure by reducing the time needed inthe radiology department. The degree of accuracy provided by theinvention is critical because there are patient consequences to acatheter in a location that is not precisely correct.

The vasculature of mammals has long been accessed to provide therapy,administer pharmacological agents, and meet other clinical needs.Numerous procedures exist in both venous and arterial systems and areselected based on patient need. One challenge common to allvascular-based therapies is health care provider access to the specificlocation or section of the vascular tree.

One common venous access procedure is central venous access. Centralvenous access is the placement of a venous catheter in a vein that leadsdirectly to the heart. Central venous catheters are ubiquitous in modernhospital and ambulatory medicine, with up to 8 million insertions peryear in the U.S. and a similar number outside the U.S. Venous accessdevices are most often used for the following purposes:

-   -   Administration of medications, such as antibiotics, chemotherapy        drugs, and other IV drugs    -   Administration of fluids and nutritional compounds        (hyperalimentation)    -   Transfusion of blood products    -   Hemodialysis    -   Multiple blood draws for diagnostic testing

Consequences of cather tip placement inaccuracies include, among otherthings:

-   Increased risk of thrombis formation-   Venous damage due to drug toxicity-   Increased risk of infection-   Additional radiation exposure

Central venous access devices are typically small, flexible tubes placedin large veins for people who require frequent access to theirbloodstream. The devices typically remain in place for long periods:week, months, or even longer.

Central venous access devices are usually inserted in one of three ways:

-   -   a) Directly. Catheters are inserted by tunneling under the skin        into either the subclavian vein (located beneath the collarbone)        or into the internal jugular vein (located in the neck). The        part of the catheter where medications are administered or blood        is drawn remains outside of the skin.    -   b) Through a port. Unlike catheters, which exit from the skin,        ports are placed completely below the skin. With a port, a        raised disk about the size of a quarter or half dollar is felt        underneath the skin. Blood is drawn or medication delivered by        placing a tiny needle through the overlying skin into the port        or reservoir.    -   c) Indirectly via a periphal vein. Peripherally inserted central        catheter (PICC) lines, unlike central catheters and ports, are        not inserted directly into the central vein. A PICC line is        inserted into a large vein in the arm and advanced forward into        the larger subclavian vein.

Central catheters and ports are usually inserted by a surgeon orsurgical assistant in a surgical suite. A PICC line can be put in atbedside, usually by a specially-trained nurse. In this latter case,confirmation by X-ray is currently required for assessing the success ofthe PICC placement. Therefore PICC procedures as currently practicedinvolve exposure to X-ray, and manipulation of the catheter increasesthe risks of infection.

Traditional, surgically-placed central catheters are increasingly beingreplaced by peripherally inserted central venous access devices. PICClines usually cause fewer severe complications than central venousaccess devices. The PICC line placement procedure is performed byinterventional radiologists to deliver long-term drug delivery,chemotherapy procedures, delivery of intravenous medications orintravenous nutrition (hyperalimentation) and taking blood samples.Insertion of PICC lines is a routine procedure in that it is carried outfor a variety of treatments, and more than once in the same patient whenthe catheter is to be left in place for any length of time. Even thoughit is routine, it is a very time and labor-intensive procedure for thehospital staff, which also makes it expensive. During the procedure thephysician or nurse places the catheter into a superficial arm vein suchas the cephalic, basilic, antecubital, median cubital, or othersuperficial vein with the goal of having the distal end of the catheterreach the superior vena cava. After entering the superficial vein aroundthe area where the arm bends (elbow), the catheter is advanced up thesubclavian vein, then the brachiocephalic vein and finally it enters thesuperior vena cava. One caveat is to make sure that the PICC line doesnot enter and remain in the jugular vein.

In addition to guiding the catheter through the vasculature, the finallocation of the catheter tip is very important to the success of theprocedure. Catheters will generally function equally well for pressuremeasurement and fluid infusion if the tip is situated in any major vein,above the heart, or below the heart. For dialysis or the infusion ofirritant/hypertonic fluids, a high rate of blood flow past the cathetertip is desirable and this requires the placement of the luminal openingin as large a vessel as possible. However, central venous catheterinstructions for use give strong warnings about the requirement forcatheter tips to lie outside the heart to avoid perforation andsubsequent pericardial tamponade. Likewise positioning the catheter tipaway from small peripheral veins is important to avoid damaging the veinwall or occluding the vein due the caustic effects of the infusingsolution. An interventional radiologist may use a fluoroscopic agent todelineate the veins in the body and subsequently verify the correctpositioning of the catheter tip using a post-operative X-ray. Currently,a post-operative X-ray is performed routinely while some studies haveshown that only 1.5% of the cases are subject to complications thatwould indeed require X-ray imaging.

Current methods for guiding PICC lines include the legacy landmarkmeasurement technique, X-ray guidance, external electromagnetic sensors,and intravascular sensors (e.g. ECG sensor). In the case of externalelectromagnetic sensors, the endovascular device is guided by assessingthe distance between an electromagnetic element at the tip of the device(e.g. a coil) and an external (out of body) receiver. This method isinaccurate because it does not actually indicate location in thevascular but instead indicates only relative position to an externalreference. In the case of ECG-guided catheters, the classic increase inP-wave size, known as “P-atriale”, is a widely accepted criterion fordetermining location of central venous catheter tips in the proximity ofthe sino-atrial node. Current methods include using a catheter filledwith saline and an ECG adaptor at the proximal end connected to an ECGsystem. This method is inaccurate because it does not indicate locationin the blood vessel but instead indicates the proximity of thesino-atrial node (SA node).

Because of known inaccuracies, all the current methods in use explicitlyrequire the use of a confirmatory chest X-ray to verify and confirmlocation of the tip of the endovascular device at the desired target inthe vasculature.

Additional approaches based on the use of non-imaging ultrasound aredescribed in U.S. Patent Pub. Nos. 2007/0016068, 2007/0016069,2007/0016070, and 2007/0016072, incorporated herein for all purposes.Limitations of an approach based exclusively on measuring right-atrialelectrocardiograms have been described in the literature, for example,in [1]: W. Schummer et al., Central venous catheters—the inability of‘intra-atrial ECCG’ to prove adequate positioning, British Journal ofAnaesthesia, 93 (2): 193-8, 2004.

What is needed is a guidance system and method that overcome the aboveand other disadvantages of known systems and methods.

In view of the variable nature of physiological signal information usedduring endovascular positioning and guidance, what is needed are methodsand apparatuses to optimize the use of physiological signal informationand take into account the variable accuracy and usefulness of the signalinformation.

What is needed is a guidance system and method that can accuratelyposition a device in irregular vascular environments such as thevasculature of patients with an aneurysm or arrhythmia.

What is needed is increased accuracy of the catheter tip placementwithout additional X-rays and manipulation of the catheter.

SUMMARY OF THE INVENTION

An aspect of the invention includes an endovenous access and guidancesystem enabled with artificial intelligence capabilities. The systemincludes a transducer on a distal end of an endovascular instrument, acontrol system connected to the transducer, the control system beingconfigured to generate and receive at least one acoustic signal usingthe transducer, a pre-processor containing computer-readableinstructions for manipulating the acoustic signal input to extractinformation related to one or more desired parameters, a processorconfigured to evaluate the acoustic features to generate an outputrelated to guidance of the instrument, and an output device fordisplaying an indication of the output generated by the processor. Theprocessor may evaluate the information using artificial intelligence andinference rules, comparisons to information in a database,probabilities, among others. The system may use an electrical signalfrom, for example, the heart as a confirmation input. Further disclosedis a method of navigating and positioning an endovascular device in avasculature, and more specifically, in a blood vessel. In variousembodiments, the acoustic signal comprises a non-imaging ultrasoundsignal.

In various embodiments, the positioning system further includes asensing electrode mounted on the instrument, the sensing electrode beingconnected to the control system and configured to measure and/or detectelectrical signals from the heart. The control system may be configuredto receive an electrical signal from the sensing electrode. Thepre-processor may contain instructions for manipulating the receivedelectrical signal to extract information related to one or more desiredelectrical features. The computer-readable set of inference rules maycontain an inference rule to evaluate the one or more electricalfeatures. In various embodiments, the processor evaluates the one ormore electrical features to confirm the output related to the guidanceor a position of the instrument within a blood vessel.

In various embodiments, the computer-readable set of rules comprises arule to evaluate whether a power level of the acoustic signal is below athreshold. In various embodiments, the computer-readable set of rulescomprising a rule to evaluate whether an antegrade flow in the bloodvessel is dominant over a retrograde flow in the blood vessel. Antegradeflow in the blood vessel is flow in the normal direction of flow, whichis generally away from the heart in the arterial system and towards theheart in the venous system. Retrograde flow in the blood vessel is flowin the opposite direction of normal flow, i.e. towards the heart in thearterial system or away from the heart in the venous system. In variousembodiments, the computer-readable set of rules comprises a rule toevaluate whether a retrograde flow in the blood vessel is dominant overan antegrade flow in the blood vessel. In various embodiments, thecomputer-readable set of rules comprises a rule to evaluate whether alow frequency signal dominates both an antegrade flow in the bloodvessel and a retrograde flow in the blood vessel.

In various embodiments, the control system is configured to synchronizethe acoustic signal and the electrical signal.

In various embodiments, the computer-readable set of rules comprises arule to evaluate a P-wave relative to a reference.

In various embodiments, the output is related to the guidance orposition comprises an indication of the most probable condition selectedfrom the group consisting of: instrument moving in a desired direction,instrument moving in an undesired direction, and instrument positionedin a desired location.

In yet another embodiment, the system is configured such that theprocessor incorporates a predetermined set of processing rules orinference statements to process in vivo non-image based ultrasoundinformation and intravascular electrocardiogram signals of thevasculature system of the patient provided by the sensors to indicate inthe output information the location or proximity of the sensors to astructure within the vasculature of the patient.

In various embodiments, the processor contains a member selected fromrules, functions, relationships, and combinations of the same used todetermine the probable location and/or movement of the device within thebody.

In various embodiments, the system includes a pre-processor configuredto pre-process physiological signals to provide feature information asinputs to the processor. Exemplary features useful in the positioningschemes described herein include: in vivo non-image based ultrasoundinformation at a particular frequency, energy level, or timing within aportion of a cardiovascular cycle; a portion of an intravascularelectrocardiogram signal, a blood flow direction, a blood flow velocity,e.g., the highest, the lowest, the mean or the average velocity, a bloodflow signature pattern, a blood flow characteristic at a particularfrequency, a pressure signature pattern, A-mode information, apreferential non-random direction of flow, the shape of the differentwaveforms and complexes charactering the intravascularelectrocardiogram, e.g., P-wave, QRS complex, T-wave, the peak-to-peakamplitudes, the absolute and relative amplitude changes and otherdistinctive elements of the intravascular ECG. Such parameters can bepre-processed as a feature for use in the fuzzy controller eitherindividually or in combination. In one specific example, the signals arepre-processed to provide inputs to the processor based on P-wave changesindicative of the proximity of the sinoatrial node near the caval-atrialjunction and together with the venous blood flow signature patternindicative of the caval-atrial junction. In another specific example,the signals may be pre-processed to identify behavior of a feature intime indicative of location in the vasculature, e.g. evident pulsatilevariations of the blood flow signature pattern may be indicative of alocation in the internal jugular vein.

Another aspect of the invention includes a method for positioning aninstrument in the vasculature of a body. The method includes inserting asystem including an endovascular device and at least one transducer intothe lumen of a patient, transmitting an acoustic signal, pre-processingthe reflected signal to extract information related to one or moredesired features, and processing the information as an input to producean output related to guidance of the instrument within a blood vessel ora position of the instrument within the blood vessel. The system mayinclude any of the features and configurations described above. Invarious embodiments, the method includes displaying an output comprisingan indication of the most probable condition selected from the groupconsisting of: instrument moving in a desired direction, instrumentmoving in an undesired direction, and instrument positioned in a desiredlocation. In various embodiments, the method includes advancing theinstrument in a blood vessel based on the output.

Another aspect of the invention includes a positioning system. Thepositioning system includes a transducer for mounting on a distal end ofan endovascular instrument; a control system connected to thetransducer, the control system being configured to generate and receivean acoustic signal using the transducer; a pre-processor receiving theacoustic signal as an input, the pre-processor containingcomputer-readable instructions for manipulating the signal input toextract one or more acoustic features from the signal input; a processorconfigured to receive the one or more extracted features, the processorcontaining a computer-readable set of rules to evaluate the extractedfeatures using the rules to generate an output related to guidance ofthe instrument within a blood vessel or a position of the instrumentwithin the blood vessel; and an output device for displaying anindication of the output generated by the processor.

In some embodiments, the positioning system further includes a sensingelectrode for mounting on the instrument, the sensing electrode beingconnected to the control system; wherein the control system is furtherconfigured to receive an electrical signal from the sensing electrode,and wherein the pre-processor further contains instructions formanipulating the received electrical signal to extract one or morefeatures related to the electrical signal; and/or wherein thecomputer-readable set of rules contains a rule to evaluate the one ormore electrical features.

In some embodiments, the acoustic signal includes a non-imagingultrasound signal. In some embodiments, the processor evaluates the oneor more electrical features to confirm the output related to theguidance or a position of the instrument within a blood vessel.

In some embodiments, the electrical signal comprises an ECG signal, anEMG signal, and/or an EEG signal.

In some embodiments, the computer-readable set of rules contained in theprocessor includes artificial intelligence programming; evaluates theextracted features based on at least one of inference rules, an expertsystem, a neural network, and logic; includes a rule to evaluate whethera power level of the acoustic signal is below a threshold; includes arule to evaluate whether an antegrade flow in the blood vessel isdominant over a retrograde flow in the blood vessel; includes a rule toevaluate whether a retrograde flow in the blood vessel is dominant overan antegrade flow in the blood vessel; and/or includes a rule toevaluate whether a low frequency signal dominates both an antegrade flowin the blood vessel and a retrograde flow in the blood vessel.

In some embodiments, the control system is configured to synchronize theacoustic signal and the electrical signal.

In some embodiments, the computer-readable set of rules further includesa rule to evaluate a P-wave in the received electrical signal relativeto a reference. In some embodiments, the rule to evaluate a P-wave inthe received electrical signal relative to a reference further includesproviding an output when the P-wave in the received electrical signal iselevated above the reference; providing an output when the P-wave in thereceived electrical signal is at or below the reference; and/orproviding an output when the P-wave in the received electrical signal isbiphasic.

In some embodiments, the output related to the guidance or a positionincludes one of a plurality of states, each state related to apredetermined set of conditions of instrument movement or position; andan indication of the most probable condition selected from the groupconsisting of: instrument moving in a desired direction, instrumentmoving in an undesired direction, and/or instrument positioned in adesired location. In some embodiments, the indication of the instrumentmoving in a desired direction is different from the indication of theinstrument positioned in a desired location.

In some embodiments, the one or more features related to the electricalsignal corresponds to a pre-selected portion of a regular electricalwave produced by the body; a pre-selected portion of an irregularelectrical wave produced by the body; and/or a pre-selected portion ofan electrical wave produced by a body having arrhythmia. In someembodiments, the electrical wave is an electrocardiogram and thepre-selected portion is an RS amplitude; an electrocardiogram and thepre-selected portion is an electrocardiogram segment; and/or anelectrocardiogram and the pre-selected portion is an electrocardiograminterval.

In some embodiments, the one or more acoustic features corresponds to aratio of a retrograde power of the flow in the blood vessel to anantegrade power of the flow in the blood vessel during a single ECGcycle; a ratio of a low frequency flow power to a high frequency flowpower; an acoustic signal obtained during a portion of a heart beat; theportion of a heart beat during the occurrence of retrograde flowproduced by atrial contraction; the portion of a heart beat during theoccurrence of antegrade flow during systole; the portion of a heart beatduring the occurrence of retrograde flow at the end of systole; and/orthe portion of a heart beat during the occurrence of antegrade flowduring diastole.

In some embodiments, the one or more features related to the electricalsignal corresponds to a portion of an QRS complex; a ratio of amagnitude of a P-wave measured by the sensing electrode and a magnitudeof a P-wave measured by an external electrode; and/or an indication ofthe presence of a biphasic P-wave.

Another aspect of the invention includes a method of positioning anendovascular instrument in a vasculature. The method includes insertingthe system of any one of the embodiments discloses herein into the lumenof a patient and advancing the device based on the output.

Another aspect of the invention includes a method of positioning anendovascular instrument in a vasculature. The method includes insertinga system including an endovascular device and at least one transducerinto the lumen of a patient; transmitting an acoustic signal within thelumen; pre-processing a reflected signal to extract one or more acousticfeatures; and processing the one or more acoustic features using acomputer readable set of rules to produce an output related to guidanceof the instrument within a blood vessel or a position of the instrumentwithin the blood vessel.

In some embodiments, the processing is performed based on a predefinedset of inference rules related to one of a set of navigation states;based on a predefined set of probabilities related to one of a set ofnavigation states; and/or based on a comparison of the one or moreparameters to a predefined set of parameters in a database.

In some embodiments, the method further includes displaying the outputrelated to guidance of the device within the blood vessel or a positionof the instrument within the blood vessel.

In some embodiments, the output comprises an indication of the mostprobable condition selected from the group consisting of: instrumentmoving in a desired direction, instrument moving in an undesireddirection, and instrument positioned in a desired location. In someembodiments, the desired direction is towards the heart and/or with aflow of blood returning to the heart, and the undesired direction isaway from the heart and/or is against a flow of blood returning to theheart. In some embodiments, the desired location is within a lower thirdof the superior vena cava; proximate to the caval atrial junction;and/or within the superior vena cava proximate to the caval atrialjunction.

In some embodiments, the method further includes manipulating the devicein the blood vessel in response to the output. In some embodiments, themanipulating step further includes withdrawing the instrument and/oradvancing the instrument.

Another aspect of the invention includes a computer readable storagemedium. The computer readable medium includes a program that can beexecuted by a processor to perform a method for positioning anendovascular instrument in a vasculature. The method includesmanipulating a reflected acoustic signal from a sensor on the instrumentpositioned within a blood vessel to extract one or more acousticfeatures from the acoustic signal; manipulating an electrical signalfrom a lead on the instrument positioned within a blood vessel toextract one or more electrical features from the electrical signal;generating an output related to guidance or a position of the instrumentwithin the blood vessel using a computer readable set of rules toevaluate the one or more extracted features; and displaying one of apredetermined number of indications of guidance or positioncorresponding to the output.

In some embodiments, the computer readable set of rules to evaluate theone or more extracted features includes one or more predefinedmembership functions that indicate one or more positional states of theinstrument.

In some embodiments, the method further includes inputting the extractedfeatures into the one or more predefined membership functions and forgenerating one or more scores that indicate the likelihood of membershipin one or more positional states; weighting the extracted features orone or more membership functions before generating one or more scores;selecting the highest score and determining the positional state basedon the highest score. In some embodiments, weighting the extractedfeatures or one or more membership functions includes applying weightingfactors to the extracted features or one or more membership functions.In some embodiments, the weighting factors apply less weight to anextracted feature or one more membership function based on a weakacoustic or electrical signal. In some embodiments, the weightingfactors apply more weight to an extracted feature or one more membershipfunction based on a strong acoustic or electrical signal.

In some embodiments, one score of the one or more scores relatesextracted acoustic features to the direction of movement of theinstrument relative to flow in the vasculature; to the overall flowenergy in the vasculature measured by the sensor; and/or to the overallflow velocity in the vasculature measured by the sensor.

In some embodiments, the one or more acoustic features corresponds to aratio of a low frequency flow power to a high frequency flow power; toan acoustic signal obtained during a portion of a heart beat; to theportion of a heart beat during the occurrence of retrograde flowproduced by atrial contraction; to the portion of a heart beat duringthe occurrence of retrograde flow at the end of systole; and/or to theportion of a heart beat during the occurrence of antegrade flow duringdiastole.

In some embodiments, the one or more electrical features corresponds toa portion of an QRS complex; to a ratio of a magnitude of a P-wavemeasured by the sensing electrode and a magnitude of a P-wave measuredby an external electrode; and/or to an indication of the presence of abiphasic P-wave.

Another aspect of the invention includes a method of determining aposition of a medical device in the vasculature of a patient. The methodincludes transmitting a signal in the vasculature comprising anultrasound signal from a distal end of a device; receiving a reflectedultrasound signal; extracting an ultrasound feature from the reflectedultrasound signal; receiving an electrical signal from a lead on thedevice; extracting an ECG feature from the received electrical signal;calculating a plurality of indicator scores using the extractedfeatures; and identifying a positional state by comparing the indicatorscores. In some embodiments, each feature infers a distinct position inthe vasculature.

In some embodiments, the calculating step further includes inputting theextracted features into a plurality of indicator equations representingpositioning probabilities. In some embodiments, the indicator equationscorrespond to membership functions. In some embodiments, the indicatorequations further include applying a weighting factor related to theextracted feature used in the indicator equation.

In some embodiments, the identifying step further includes selecting thepositional state that corresponds to the highest indicator score.

In some embodiments, the calculating step further includes solvingpreset equations based on a correlation between an extracted feature anda probability of a particular position or state of navigation of thedevice.

In some embodiments, one indicator score in the plurality of indicatorscores relates extracted acoustic features to the direction of movementof the device relative to flow in the vasculature; acoustic features tothe overall flow energy in the vasculature measured by the sensor;and/or acoustic features to the overall flow velocity in the vasculaturemeasured by the sensor.

Although certain aspects or features of the invention have beendisclosed in connection with certain embodiments, it is understood thatthese aspects or features can be incorporated with any of the otherembodiments disclosed herein, as appropriate.

The systems and methods of the present invention have other features andadvantages which will be apparent from or are set forth in more detailin the accompanying drawings, which are incorporated in and form a partof this specification, and the following Detailed Description of theInvention, which together serve to explain the principles of the presentinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 illustrates an overview of an endovascular device guiding systemand method disclosed in accordance with the invention.

FIG. 2 illustrates an endovascular device with multiple sensors.

FIGS. 3A-3B illustrate an optional intravascular ECG electrode which canbe used for steering and moving the endovascular member away from thevessel wall.

FIGS. 4A-4C illustrate the concept of a removable sensor core, whereby astylet with integrated sensors can be inserted into and removed from anendovascular device like a catheter at any time.

FIGS. 5A-5B illustrate an embodiment of integrated sensors in anendovascular device with a braided shaft and atraumatic tip.

FIG. 6 is a block diagram of the software/processing system of FIG. 1.

FIG. 7 illustrates a graphical user interface displaying blood flowinformation, intravascular ECG signals, their correlation, and cathetertip location information based on the processing method in accordancewith the invention. FIG. 7 also illustrates the use of A-mode imagingfor clot identification inside the blood stream or inside anendovascular member.

FIGS. 8A-8D illustrate a simplified user interface corresponding to theuser interface of FIG. 7 and using blood flow information, optionalintravascular ECG signals, and their correlation to display if theendovascular member is advancing towards the caval-atrial junction andsinoatrial node, if the endovascular member is advancing away from thecaval-atrial junction and sinoatrial node, or if the endovascular memberis at the caval-atrial junction proximal to the sinoatrial node.

FIG. 9 is a block diagram of an endovascular guidance system inaccordance with the invention, illustrating pre-processor and processorcircuitry for manipulating a Doppler signal and optional ECG signal.

FIG. 10 is a block diagram representing the flow of data in the systemof FIG. 9.

FIG. 11 is a flow chart of the pre-processing of signal data of FIG. 10to obtain three Doppler features in accordance with the invention.

FIG. 12A illustrates an intravascular ECG signal used to correlategating of the acquisition or processing of the blood flow information ofFIG. 11 to the heart function.

FIG. 12B illustrates an intravascular ECG signal indicating theamplitude of the RS portion of the signal in a brachial vein portion andin the portion of the caval atrial junction (CAJ).

FIG. 13 is a flow chart of the pre-processing of signal data of FIG. 11to obtain Doppler feature 1a (DF1a).

FIG. 14 is a flow chart of the pre-processing of signal data of FIG. 11to obtain Doppler feature 2.

FIG. 15 is a flow chart of the pre-processing of signal data of FIG. 11to obtain Doppler feature 3.

FIG. 16 is a block diagram of the system of FIG. 9, illustratingreceiving information related to the pre-processed feature as inputs andproviding a result based on membership functions.

FIG. 17 is a flow chart of the method of using the system of FIG. 9 toguide an endovascular device to a desired destination in accordance withthe invention.

FIG. 18 is a block diagram of optional confirmation sources that may beinput to the pre-processor according to the method of FIG. 17.

FIG. 19 illustrates an endovascular device within the vasculature atvarious locations according to the method of FIG. 17.

FIGS. 20 and 21 are various views of the heart and surroundingvasculature.

FIG. 22 illustrates the optional use of an intravascular ECG signal togate or trigger the acquisition or processing of the blood flowinformation.

DETAILED DESCRIPTION OF THE INVENTION

For convenience in explanation and accurate definition in the appendedclaims and following description, the terms “up” or “upper”, “down” or“lower”, “inside” and “outside” are used to describe features of thepresent invention with reference to the positions of such features asdisplayed in the figures.

Patient data has long been used for diagnostic and therapeutictechniques. Various features may be measured, monitored, and analyzedfor myriad purposes such as identifying a medical condition orperforming a medical procedure. Improvements in medical technology haveled to the use of patient monitoring for far more applications. Theadvance of computer technology and its integration into the medicalfield has significantly expanded the applications for analysis ofpatient data. For example, U.S. Pat. No. 6,179,782 to Cucè, incorporatedherein for all purposes by reference, discloses a system for classifyinga patient and identifying a medical indication by coupling a fuzzy logicprocessor to a conventional blood pressure cuff monitoring arterialpressure.

The broad class of systems and methods for monitoring and collectingpatient data can be categorized based on several distinctions. For one,the system may either collect data for analysis at least somewhatcontemporaneously or store the data for analysis later. For another, thesystem may use the patient data for therapeutic, surgical, or diagnosticpurposes. Of course, some system and methods can be used for multiplepurposes and in multiples ways.

Various aspects of the invention relate to a system and methods fornavigating and positioning a device in the body. Various aspects of theinvention relate to a system and methods for navigating and positioninga device in the vasculature. The use of patient data for navigating andpositioning devices in the vasculature has long been used. Aconventional technique involves placing a device in the superior venacava (SVC) just short of the right atrium. In a typical procedure, thedevice is inserted into the body (e.g. percutaneously) and moved towardsthe heart. An ECG signal is displayed on a monitor as the device moves.The user compares the P-wave on the monitor and identifies a particularlocation by identifying changes to the P-wave. An example of this methodis disclosed by U.S. Pat. No. 5,078,678 entitled “Method and Apparatusfor Locating a Catheter Adjacent to a Pacemaker Node of the Heart,” toKatims, the entire contents of which are incorporated herein for allpurposes.

Conventional methods for navigating and positioning devices in thevasculature have several drawbacks. A significant limitation is the factthat the system relies on the user to notice even minute changes to theP-wave. The user must recognize specific and nuanced P-wave shapes,amplitudes, and trends, all while busy performing the actual procedure.Additionally, the technique is useful for identifying a specificlocation—the SVC at an entrance to the right atrium—but does notgenerally provide for the general positioning of devices in otherlocations. This is a problem in that the lower third of the SVC isconsidered to be more optimal for many applications (e.g. dilation anddrug delivery) than the bottom of the SVC. The system also does notprovide navigation. The user has no indication of location. The usermerely recognizes a shift when a target is passed and then has towithdraw the device back to the target.

Various aspects of the invention relate to use of a plurality of inputvariables related to the body and its functioning for therapy anddiagnosis. In the context of the cardiovascular system, for example,many inputs can be used for a single application. Many inputs used bythe system in accordance with aspects of the invention are considered asnoise or useless by conventional systems and techniques. The systemgenerally makes use of sophisticated processing techniques to read,interpret, and analyze complicated information for specific purposes.For example, conventional systems typically cannot be used in the venousvasculature because the blood flow is so turbulent and complicated as tobe wholly indecipherable by a user.

Various aspects of the invention are directed to collecting the hugeamounts of data long considered as an impediment (e.g. noise) andadvantageously using the data to improve performance and/or accomplishtasks previously considered impossible. For example, various aspects ofthe invention relate to a non-imaging system and methods for navigatingand positioning a device in the venous vasculature as opposed to thearterial vasculature. The system may make use of intravenous informationwithout the use an X-ray, fluoroscopy, and conventional methods. Variousaspects of the invention relate to a system and methods for navigatingand positioning a device in the body using a plurality of informationrelated to the patient, and more specifically, related to the patient'scardiovascular system.

In various respects, the present invention provides new methods, devicesand systems for intravascular guidance and placement of endovasculardevices based on the recognition of patterns in the signals fordifferent physiological features and correlation of those signalpatterns.

Aspects of the current invention overcome the above describedlimitations and provided accuracy by applying a guidance system to theobtained physiological signals. The guidance system of the inventiontakes into account the variable nature of the obtained physiologicalfeatures, the relationship of one or more physiologic signals tospecific locations in the vasculature, and the degree of accuracyprovided during the different phases of endovascular navigation. Theoutput of the positioning system provides indications to a user in theform of navigation instructions and/or position information.

The exemplary system will now be described generally with reference toFIGS. 1, 2, 3A, 3B, 4A-4C, 5A, 5B, 6, 7, and 8A-8D. Further details ofthe system will be provided below.

An exemplary device in accordance with various aspects of the inventionis shown. Embodiments of the present invention include a pre-processorfor obtaining one or more physiological signals and pre-processing theobtained signals to extract desired features and provide inputs to aprocessor. Various aspects of the pre-processor are similar toconventional signal processing and medical diagnostic systems. U.S. Pat.No. 6,007,491 to Ling et al., incorporated herein for all purposes byreference, discloses a cardiac output monitor. The system analyzes ablood pressure waveform in part by extracting desired featureparameters. The system receives the blood pressure waveform as an input,digitizes the input, and then extracts selected blood pressure featuresfor use as inputs in a fuzzy logic model.

An exemplary pre-processor is shown in FIG. 9. The pre-processorincludes hardware and software. The software may be implemented in theexemplary personal computer (PC). The other features shown in the figuregenerally relate to the hardware for the sensors and pre-processorhardware. The software may be configured to pre-process the raw data.The hardware may be configured to extract specified feature informationfrom the signal data processed by the software. The pre-processing mayinclude, but is not limited to, conversion of a Doppler or an ECG signalfrom the time domain to the frequency domain, frequency to time domain,amplification, filtering, analog-to-digital conversion, and partitioningof an ECG waveform to extract one or more ECG features, partitioning ofan acoustic waveform to extract one or more acoustic features. Thepre-processing can be performed on any inputs or features or signaldescribed herein, such as Doppler signals, ECG signals or other naturalor artificial sources, for example.

The features are transmitted to the processor as inputs. The processorthen evaluates the pre-processed inputs to obtain precise and accuratelocation and/or guidance information for output and display to the user.The processor may process the pre-processed inputs using artificialintelligence such as a predetermined set of processing rules, inferencestatements, and the like.

Various functions of the pre-processor and processor are similar tothose employed by existing medical diagnostic devices. U.S. Pat. No.7,627,386 to Mo et al., incorporated herein for all purposes byreference, discloses an ultrasound system making use of a neural networkprocessor and fuzzy logic controller. The Mo system employs thedifferent processors and controllers to optimize the ultrasound imagesfor clinical diagnosis. U.S. Pat. No. 6,179,781 to Phillips,incorporated herein for all purposes by reference, discloses a processorthat assigns weights to feature parameters to improve the accuracy of amedical diagnostic ultrasound apparatus. U.S. Pat. No. 6,179,782 toCuce, incorporated herein for all purposes by reference, discloses useof a fuzzy logic processor to more accurately measure arterial pressure.U.S. Pat. No. 7,966,061 to Al-Abed et al., incorporated herein for allpurposes by reference, discloses a system for detecting a sleepdisorder. The Al-Abed system uses statistical analysis to formulateinference rules for a fuzzy logic processor which analyzes an externalECG waveform. These and other references are directed to differentpurposes, signal data, and patient populations than the invention;however, these references are representative of the integration ofcomputer processing techniques into the medical diagnostics field.Various aspects of the invention are directed to improve processingtechniques. Various aspects of the invention are directed analyzinghemodynamic data for navigation and positioning within the vascularsystem, and in some respects, the venous vasculature.

As will be discussed in greater detail below, the pre-processor and/orprocessor in accordance with the invention may employ artificialintelligence features. “Artificial intelligence” is used broadly torefer to a large collection of advanced processing techniques including,but not limited to, logic (e.g. fuzzy logic, Bayesian probability,two-valued logic, and sentential logic), probabilistic reasoning, anexpert system, one or more pattern recognition technique, a neuralnetwork, an inference engine, classifiers, and combinations of the same.

An input signal is obtained from the body and used to determine thelocation or relative movement of a device positioned within the body. Invarious embodiments, two different input signals are obtained from thebody. The input signals are typically amplified, filtered or convertedas is typical in the digitalization of analog signals and other signalprocessing techniques. These collected signals are then pre-processed toproduce one or more parameter inputs for use in a processor/controller.

In various embodiments, the system acquires two or more signals and atleast one of the signals is used as a confirmation signal. For example,the system may acquire a Doppler signal and an ECG signal. The systemmay process one of the signals and output a result. The result may beconfirmed by independent processing of the other signal. For example,the system may rely primarily on Doppler-based guidance but use the ECGsignal to confirm the Doppler-based result. In this way the system mayprovide improved confidence levels.

One will appreciate from the description herein that the system mayacquire and process signals over a variety of time periods. In oneexample, ECG and Doppler signals are analyzed over time intervals thatrange from less than one heart beat (i.e., during a portion of a QRScomplex or during the same portion of a QRS complex on sequentialheartbeats) to a heart beat during patient inspiration, expiration, orduring a portion of a respiration cycle or sequential respirationcycles. Multiple time intervals could be analyzed together using variousmembership functions.

Endovascular Member with Sensors for Guidance

FIGS. 1-2 illustrate an exemplary endovascular access and guidancesystem 100 including a catheter is shown. The system and exemplarycatheter are similar in many respects to those described in U.S. PatentPub. No. 2009/0005675 to Grunwald et al., the entire contents of whichis incorporated herein for all purposes.

The exemplary device is configured to obtain two different physiologicalsignals from the body, in particular, a Doppler signal (an in vivo,non-image-based ultrasound signal) and an ECG signal. One willappreciate from the following description, however, that the system mayoperate using only a Doppler signal or only an ECG signal. One willfurther appreciate that the system is not limited to Doppler or ECG;other signals as will be understood by one of skill from the descriptionherein may be used. Examples of other measurable information that may beuseful in the invention include, but are not limited to, oxygensaturation, cardiac output, heart rate, blood pressure, temperature, andrespiration rate.

The illustrated system 100 includes a peripherally inserted centralcatheter (PICC). One will appreciate that the system may be paired withother medical devices such as an endoscope. The exemplary catheterincludes an elongate body 105 with a proximal end 110 and a distal end115. The exemplary elongate body 105 is any of a variety of endovasculardevices adapted for insertion into and navigation through thevasculature of the patient 1. FIG. 1 illustrates the distal end 115inserted into the basilic vein 6, for example. The expected path oftravel (dashed line 20) in this illustrative example is into a portionof the heart 20 or within the superior vena cava 14 in proximity to thesinoatrial node (SA node) 8. The aorta 3, the pulmonary arteries, thepulmonary veins 11, the jugular veins 10, the brachiocephalic vein 12,the inferior vena cava 16, and the atrioventricular node (AV node) 9 arealso represented in this view.

Not shown in FIG. 1, but further described below, the exemplary elongatebody 105 includes a first ultrasound sensor and one or more optionalsensors for measuring physiological features in the body. In someembodiments, the first sensor is a non-imaging ultrasound transducer 120on the elongate body 105 configured to provide in vivo non-image basedultrasound information of the vasculature of the patient 1. In someembodiments, the one or more optional sensors is an endovascularelectrocardiogram lead on the elongate body 105 in a position such that,when the elongate body 105 is in the vasculature, the endovascularelectrocardiogram lead electrical sensing segment provides an in vivoelectrocardiogram signal of the patient 1. In various embodiments, theelongate body 105 includes two or more ultrasound sensors spaced apartby a specified distance. FIG. 1 illustrates the use of a secondelectrocardiogram sensor that is outside of the vasculature. Theelectrode 112 is positioned external to the vasculature of the patient1. The electrode 112 detects electrocardiogram information that istransmitted via lead 111 to the processor 140. In various embodiments,the system includes a plurality of external ECG sensors. For example,although only a single lead or electrode is shown in shown in FIG. 1 forillustrative purposes, it is understood that a plurality of external ECGelectrodes can be used, such as a 3 electrode system that is placed toform a triangle around the patient's heart. In other embodiments, astandard 5 electrode system can be used. Similarly, the signals may begenerated by one or more structures in the body or external to the body.

In various embodiments, in place of the electrode 112, or in addition tothe electrode 112, another electrocardiogram sensor may be placed on theelongate body 105. More than one electrocardiogram sensor may beprovided on the elongate body. In this case, the processor 140 wouldalso be configured to receive, process, compare and correlate theelectrocardiogram information from the additional electrocardiogramsensor (or other sensors) provided by the elongate body 105.

The electrocardiogram leads or sensors on the elongate body 105 may alsobe placed relative to the elongate body 105 and to one another in orderto obtain a target electrocardiogram signal and a baselineelectrocardiogram signal in order to facilitate the position andlocation capabilities of the guidance system 100. The target andbaseline electrocardiogram information may be related to one or more of:(a) electrical activity of the heart including all or a portion of anelectrocardiogram (ECG); (b) electrical activity of the brain includingall or part of an electroencephalogram (EEG); and (c) electricalactivity of a muscle or muscle group including all or part of anelectromyogram (EMG) related to that muscle or muscle group. Additionaldetails of the sensors and the various alternative configurations of theelongate body 105 are described below with respect to at least FIGS.2-5B.

The system 100 also includes an output device 130 configured to displaya result of information processed by the processor 140. The displaydevice may, like the processor 140, include capabilities found inconventional display devices among other capabilities. The displaydevice 140 of the invention differs from the conventional display inthat the display is configured to display information related to theunique processing and results determined by processor 140. Inparticular, rather than displaying acquired signal information, theoutput device displays straightforward indicators to the clinician basedon the underlying processing of the signals. Unlike conventionaldisplays, the user does not need to have considerable experienceinterpreting signal information nor engage in the time-consuming andcomplicated process of interpreting the signal information in real-time.

In one aspect, the output device 140 displays a result related to aposition of the elongate body within the vasculature of the patient. Inanother aspect, a result of information processed by the processorincludes an indication of a position or a movement of the elongate body105 within the vasculature based on in vivo non-image based ultrasoundinformation and in vivo electrocardiogram information. The display 130would be configured to display this information for a user to perceivein any suitable manner such as visually, with colors, with pictograms,with sounds or in other appropriate manners.

FIGS. 7, 8A, 8B, 8C, and 8D illustrate an alternative output devicewhereby indicators having specific shapes, sizes, and/or colors relateto the user the exact position of the device in the vasculature. FIGS.8A, 8B, 8C, and 8D illustrate the positions corresponding to eachindicator. The indicators may be any color, icon, and sound, or anyother kind of graphical, alphanumeric, and/or audible elements toindicate the tip location in an easy-to-understand manner.

The exemplary output device also displays a variety of other informationto the user such as tracing of the received Doppler signals and a meterrepresenting the relative contributions of antegrade and retrogradeflow. The exemplary output device also includes a number of controls andinstrument displays.

In an exemplary embodiment, Doppler and/or ECG signals are used todetermine the catheter tip location. In various embodiments, the systemmakes use of the fact that, during the catheter insertion, thephysiological characteristics of the input signals are different indifferent positions. In various embodiments, artificial intelligence isused to derive positional information from the sensor signals to guidethe tip to and land at optimal desired position (e.g. the lower ⅓ ofsuperior vena cava (SVC) and the catheter tip heading to atrium). Thetwo signals are amplified, sampled, and filtered along with otherappropriate pre-processing operations to render the signal informationas one or more features. These features become inputs to a processor.The processor then processes the input and outputs a result indicativeof the position and/or direction of the tip. Parameters associated withthe feature and algorithms generally include constants, coefficients andweighing factors, for example, that can be adjusted to fine tune thealgorithms.

In an exemplary Doppler channel, the transmitter center frequency isabout 11.667 MHz, outputting a burst of about 8 pulses at a pulserepetition frequency (PRF) of approximately 30 kHz. The received Dopplersignal may be amplified, sampled, down-converted or otherwiseappropriately subjected to operations to yield features used as inputsto the guidance system, and in particular, the pre-processor.

The operating frequency and PRF typically depend on the hardware and thedevice environment. The exemplary system for insertion and navigation inthe venous environment has a selected operating frequency of betweenabout 8 MHz and about 15 MHz, and in various respects between about 10MHz to about 12 MHz. In various embodiments, the operating frequency isabout 12 MHz. The operating frequency may be higher or lower dependingon the applications. For example, conventional coronary artery systemsoperate at around 20 MHz.

The PRF drives the signal generation and acquisition. Among otherthings, the PRF in combination with the operating frequency determinesthe resolution of the signal. For example, if the PRF is too low thesystem will not acquire useful data. Generally, a higher PRF providesmore flow information but emits more energy into the patient. Thus, ifthe PRF is too high the system may present a health risk to the patient.In various embodiments, the PRF is between about 30 kHz to about 45 kHz.In various embodiments, the PRF is below 60 kHz, below 50 kHz, below 40kHz, or below 30 kHz. In various embodiments, the PRF is about 30 kHz orabout 40 kHz. By contrast, the PRF needs to be significantly higher foruse in the arterial system. Typically, PRF must be around 100 kHz orhigher in the arterial system.

During the insertion, the exemplary guidance system provides fourdifferent signs or output indications: a green arrow, the blue bull'seye, a red stop indicator, and yellow bar, to guide the clinicaloperator to reach the optimal position (shown in FIGS. 7, 8A, 8B, 8C,and 8D). As will be described in greater detail below, the exemplaryprocessor is designed around the probability that the device is in oneof four navigational states. State 0, state 1, state 2, and state 3 areused to represent yellow (i.e. caution and/or more data needed), greenarrow (i.e. go forward), the blue bull's eye (i.e. landing zoneachieved), and red circle (i.e. wrong direction, pull back),respectively. The exemplary four states will be described in greaterdetail below with respect to Tables 1-6. Note that the term “zone” canbe used interchangeably with the term “state.” The system describedincludes four states for illustration purposes. One will appreciate fromthe description herein that more or less states may be provided for inthe processor.

Various aspects of the invention relate to the use ofintravascularly-measured physiological parameters for locating, guiding,and placing catheters in the vasculature. Various aspects of theinvention relate to an endovascular member assembly with built-insensors for measuring of physiological parameters such as blood flow,velocity, and pressure. Various aspects of the invention relate to anassembly for further measuring intravascular ECG.

Various aspects of the invention relate to data processing algorithmsthat can identify and recognize different locations in the vasculaturebased on the pattern of physiological parameters measured at thatlocation. FIG. 6 illustrates an exemplary software block diagram 4 forproviding the processing capabilities used by embodiments of the presentinvention.

Various aspects of the present invention relate to data processingalgorithms that can identify and recognize structures such as objects ofinterest in the vasculature or in endovascular members, for example,blood clots based on the pattern of parameters measured (e.g., A-modeand blood flow velocity). Various aspects of the invention relate to aninstrument that has a user interface which shows guiding and positioninginformation and presents the objects of interest (e.g. blood clots). Forexample, in this aspect the processor is further configured to process asignal from the non-image ultrasound transducer and to indicate in theoutput device information related to the presence of a structure in thefield of view of the non-imaging ultrasound transducer. In variousembodiments, the system can draw conclusions from the locationinformation and even make recommendations to the user.

Various aspects of the invention relate to a method of guiding andpositioning an endovascular member within the vasculature by the userbased on location information provided by the sensor-based endovascularmember. Other various aspects of embodiments the invention relate to theuse of intravascularly measured physiological parameters for locating,guiding, and placing catheters or stylets or guide wires for use asguides to particular locations within the vasculature that have beenidentified using the guided vascular access devices and systemsdescribed herein.

FIGS. 2, 3A, 3B, 4A and 4B illustrate an endovascular device 150 inaccordance with various aspects of the invention having an elongate body105 with a proximal end 110 and a distal end 115. A non-imagingultrasound transducer 120 is provided on the elongate body 105. Anatraumatic tip 121 is provided on the endovascular device 150. Theatraumatic tip 121 may also include an ultrasound lens. The ultrasoundlens may be used to shape the ultrasound signal produced by theultrasound transducer 120. In one aspect, the ultrasound lens is adivergent lens.

The endovascular device 150 also has an opening 182 in the elongate body105 and a lumen within the elongate body 105 in communication with theopening 182 and the elongate body proximal end 110. As illustrated,there may be one or more openings 182 in communication with one or morelumens or tubes 183. Also shown on the proximal end 110 are the variousconnections to the sensors and lumens in the endovascular device 150.These connections are conventional and may take any suitable form toconnect the endovascular device to the other guidance system 100components such as the processor, display or fluid delivery device. Assuch, by using additional lumens or other access features, the elongatebody 105 or endovascular device 150 is adapted to deliver a therapy tothe patient such as by delivering drugs, therapeutic or diagnosticagents through the openings 182 or between the inner and outer tubes. Inyet another alternative configuration, the elongate body 105 or theendovascular device 150 is adapted to provide endovascular access foranother device.

One will appreciate that other additional and optional sensors may beprovided on the endovascular device 150. Embodiments of the endovasculardevice 150 may contain any of a number of different sensors. The sensoris selected based on the physiological parameter to be measured and usedin the guidance, positioning and correlation methods described herein.By way of non-limiting example, the device may include an ultrasoundsensor, a conductive wire, a pressure sensor, a temperature sensor, asensor for detecting or measuring electrical potential and voltages andother sensors suited to collecting physiological information andproviding information to the processor 140 for processing in analgorithm or for other suitable form of analysis based on the techniquesdescribed herein. The sensor-based endovascular device 150 can be usedindependently to deliver a payload into the vasculature, e.g., a drug orto draw blood or it can be inserted into the one of the lumens ofanother endovascular device, e.g., a catheter. Then the entire assemblycan be inserted into the patient's body, e.g., for a PICC placementprocedure, or through a catheter 90 (shown in FIG. 4C).

Additionally or alternatively, the endovascular device 150 can beconfigured as any type of catheter, stylet, guidewire, an introducer, acombination thereof or any other type of device which allows forvascular access. The endovascular device and the correspondingconnection from the sensors to the proximal end can either be fixed inthe endovascular device, or pre-inserted and removable after procedure,or reinsertable for location verification post placement. In oneembodiment the endovascular device integrates a single lead electrodefor electrical activity monitoring. In a different embodiment, theendovascular device may integrate several electrodes (leads), forexample one at the very distal tip of the endovascular member and onemore proximal such that the distal electrode can detect the electricalactivity of the heart while the more proximal electrode can serve as areference for measuring since the more proximal electrode is closer tothe patient's skin and further away from the heart. In addition toproviding electrical mapping, the lead/electrode can be used as asteering element to steer and position the endovascular device asillustrated in FIGS. 3A, 3B, 4A and 4B.

According to the embodiments of the present invention physiologicalinformation is acquired by sensors and transmitted to a processor. Theprocessor uses algorithms which analyze and process the sensor data toprovide information on the location of the sensor core assembly and ofthe corresponding endovascular device in the patient's vasculature.Since high degree of accuracy is desired, different types ofphysiological information, ideally independent from each other, such asblood flow information and electrocardiogram information are used toaccurately characterize the direction of movement and location. In oneaspect of the present invention, the described clinical need is met bygathering physiological information regarding blood flow usingultrasound and regarding the electrical activity of the heart byacquiring endovascular electrical signals.

By way of example, the endovascular device embodiments of FIGS. 3A, 3B,5A, 5B, include an elongate body 105 that may be configured as any of acatheter, a stylet, or a guidewire that is configured for endovascularaccess. Moreover, the catheter, stylet or guidewire may be of the onepart or two part construction described herein.

The endovascular device 150 may be configured as a single structure(shown, e.g., in FIGS. 3A, 3B, 4A, 4B, 5A and 5B). The device may be aremovable device or sensor core assembly and may consist of anon-imaging ultrasound transducer mounted at the end of a piece oftubing. The tubing can be single or multi-lumen and can be made of anyof a variety of polymeric or elastomeric materials. The lumens may beused to support the sensors on the tubing or may be used for delivery oftherapeutic or diagnostic agents. One or more physiological parametermonitoring sensors may be positioned on the tubing as described herein.The endovascular device may have a two part construction as shown in theillustrative embodiment of FIG. 2 where the ultrasound transducer is ona tube (an inner tube) within another tube (an outer tube).

In the illustrative embodiment of FIG. 2, the inner tube carries theultrasound transducer. The outer tube, possibly a multi-lumen tube, hasa lumen for the inner tube. Additionally, lumens 183 are provided tocorrespond to the openings 182. The outer tube also supports theadditional sensors (one sensor 186 is shown). The wiring or otherconnections for the additional sensors 186 or electrocardiogram lead mayalso be provided with their own lumen or lumens. The proximal end 110and the various leads and lumens and other connections may be placedinto a single connector used to attach the endovascular device 150 tothe other components of the system 100.

Whether the endovascular device 150 is a single tube or a multiple tubeconstruction, the device optionally includes an additional sensor 186 onthe endovascular device for measuring a physiological parameter. In oneaspect, the additional sensor is an optical sensor and the physiologicalparameter is related to an optical property detected within thevasculature. In another aspect, the additional sensor is a pressuresensor and the physiological parameter is related to a pressuremeasurement obtained within the vasculature. In another aspect, theadditional sensor is an acoustic sensor and the physiological parameteris related to an acoustic signal detected within the vasculature.

The exemplary system includes an optional endovascular electrocardiogramlead 130 on the elongate body 105 in a position that, when theendovascular device 150 is in the vasculature, the endovascularelectrocardiogram lead 130 is in contact with blood. There are twoendovascular leads 130 in the illustrated embodiment of FIG. 2. Asshown, there is an endovascular electrocardiogram lead 130 positioned atthe elongate body distal end 115.

The electrocardiogram lead 130 contains at least one electrical sensingsegment 135. The electrical sensing segment 135 is that portion of theelectrocardiogram lead 130 that is used for detecting or sensing theelectrical activity being measured. The electrical sensing segment 135could be a portion of the lead 130 that is not insulated, it could be aseparate structure, like an electrode, that is joined to the lead 130 orit could be a structure within the endovascular device (shown in FIG.5B). In one aspect, the electrical sensing segment of an endovascularelectrocardiogram lead is positioned within 3 cm of the elongate bodydistal end 115. In another aspect, the electrical sensing segment 135 ofan endovascular electrocardiogram lead 130 is positioned within 3 cm ofthe non-imaging ultrasound transducer 120. As shown in FIG. 2, thisaspect relates to the lead 130 that extends from the distal end or tothe spacing of proximally positioned endovascular lead 130. Additionallyor alternatively, the electrical sensing segment 135 of an endovascularelectrocardiogram lead 130 is positioned proximal to the non-imagingultrasound transducer 120.

FIG. 2 also illustrates an exemplary endovascular device with anoptional second endovascular electrocardiogram lead 135 on the elongatebody 105. The second endovascular lead is shown in a position that, whenthe endovascular device 150 is in the vasculature, the secondendovascular electrocardiogram lead 130 is in contact with blood.Endovascular leads 130 (and/or the corresponding electrical sensingsegment or segments 135) may extend from the elongate body 105 as shownin FIGS. 2 and 3A or may be integral to or within the elongate body asshown in FIGS. 3B, 4A, 4B 5A, and 5B. In one embodiment, the electricalsensing segment 135 of the second endovascular electrocardiogram lead130 (the proximal electrocardiogram lead 130 in FIGS. 2 and 4B) ispositioned about 5 cm from the other endovascular electrocardiogram lead130. Alternatively, electrical sensing segment 135 of the secondendovascular electrocardiogram lead 130 is positioned about 5 cm fromthe elongate body distal end 115.

The present invention provides new methods, devices, and systems forintravascular guidance and placement of endovascular devices based onthe recognition of patterns in the signals for different physiologicalparameters and correlation of those signal patterns. In one exemplaryapplication, a catheter, such as a peripherally inserted centralcatheter (PICC) is inserted, advanced, positioned, and monitored withinthe vasculature based on the recognition of parameter information (e.g.blood flow patterns) and their correlation at the locations of interest.In various embodiments, the system optionally utilizes electrocardiogramsignals with the above parameters.

Pre-Processing and Processing System

The present invention provides a new methods, devices and systems forintravascular guidance and placement of endovascular devices based onthe recognition of patterns in the signals for different physiologicalparameters and correlation of those signal patterns to catheter tiplocations. In addition or alternatively, neural network algorithms canbe used for feature extraction, determining parameter values, and/or beused in scoring functions, as further described below.

FIG. 9 is an exemplary block diagram of at least a portion of a systemin accordance with various aspects of the invention. In variousrespects, the system of FIG. 9 is similar to the system 100 of FIG. 1and the same numbering will be used herein.

Various components of system 100 are similar to conventional ultrasoundcontrol systems. Examples of ultrasound control systems are described inthe following patents: U.S. Pat. No. 6,896,658 to Ji et al. entitled“Simultaneous Multi-mode and Multi-band Ultrasonic Imaging”; U.S. Pat.No. 6,251,073 to Imran et al. entitled “Miniaturized UltrasoundApparatus and Method”; U.S. Pat. No. 5,492,125 to Kim et al. entitled“Ultrasound Signal Processing Apparatus”; U.S. Pat. No. 6,561,979 toWood et al. entitled “Medical Diagnostic Ultrasound System and Method”;and U.S. Pat. No. 5,477,858 to Norris et al. entitled “Ultrasound BloodFlow/Tissue Imaging System”; related to Doppler ultrasound U.S. Pat. No.4,324,258 to Huebscher et al. entitled “Ultrasonic Doppler Flowmeters”;U.S. Pat. No. 4,143,650 to Hatke entitled “Directional DopplerUltrasound Systems for Biosignal Acquisition and Method of Using theSame”; U.S. Pat. No. 5,891,036 to Izumi entitled “Ultrasonic WaveDoppler Diagnosing Apparatus”; related to guidance U.S. Pat. No.5,220,924 to Frazin entitled “Doppler-Guided Retrograde Catheterizationusing Transducer Equipped Guide Wire”; U.S. Pat. No. 6,704,590 toHaldeman entitled “Doppler Guiding Catheter using Sensed BloodTurbulence Levels”; U.S. Pat. No. 5,311,871 to Yock entitled “Syringewith Ultrasound Emitting Transducer for Flow-directed Cannulation ofArteries and Veins”; U.S. Pat. No. 6,612,992 to Hossack et al. entitled“Medical Diagnostic Ultrasound Catheter and Method for PositionDetermination Related to Tracking Method”; U.S. Pat. No. 5,785,657 toBreyer et al. entitled “Blood Flow Measurement Device”; and related topressure estimation U.S. Pat. No. 5,749,364 to Sliwa Jr. et al. entitled“Method and Apparatus for Mapping Pressure and Tissue Properties”, theentire contents of which patents are hereby incorporated herein for allpurposes.

The system 100 includes a pre-processor 139 and processor 140 configuredto receive and process a signal from the non-imaging ultrasoundtransducer and a signal from the optional endovascular electrocardiogramlead. In the embodiment illustrated in FIGS. 6 and 9, the hardware andthe software of the pre-processor are separate. The pre-processorsoftware is implemented on the same device (e.g. a personal computer ormicroprocessor) as the processor software. The other pre-processingfunctions are handled by the hardware. The hardware may also includeembedded software or firmware. In other embodiments, the preprocessorcan be entirely software or entirely hardware.

Referring to FIG. 9, the system 100 includes a stylet-ECG interface 201having one or more sensors. A programmable pulse sequence generatorincluding a pulser 203, pulser drive 205, and pulser control 207generates electronic signals, such as electronic pulses, that drive theultrasound sensor. A transmit-receive switch 210 controls the interfaceand sends/receives signal data to and from the sensor. The transmissionand reception functions are controlled by pulser 203, pulse drive 205, afield programmable gate array (FPGA) 213, and a digital signal processor215. The exemplary signals are individually delayed depending on themode of processing and other factors. In one example, the generatedwaveform for the sensors depends on the operating mode. A-scan, Doppler,etc. can be selected according to the desired mode. In an exemplaryembodiment, an A-scan is generated about every 10 ms. In an exemplaryembodiment, a sensor is driven with a Doppler pulse sequence fired at afrequency referred to as pulse repetition frequency (PRF). In variousembodiments, the PRF is about 40 kHz. The system may make use ofpulsed-wave (PW) or continuous-wave (CW) functions. Further informationregarding parametric waveform generation and similar concepts arediscussed in U.S. Pat. No. 6,896,658 to Ji et al for Simultaneousmulti-mode and multi-band ultrasonic imaging and U.S. Pat. No. 6,551,244to Gee for Parametric transmit waveform generator for medical ultrasoundimaging system, the entire contents of which are incorporated herein forall purposes.

The transmit-receive switch 210 provides acquired data to the othercomponents of the system. In an exemplary embodiment, the systemincludes a plurality of Doppler sensors and the transmit-receive switchincludes a multiplexer to couple electrical signals from generator toeach of the respective sensors (e.g. 120 in FIG. 2). The exemplarysensors generate a single divergent ultrasound beam by transforming theelectrical energy into mechanical acoustic waves. The exemplary acousticwaves are between about 5 MHz and about 15 MHz.

The sensor receives a reflected signal (e.g. an echo) and transforms thehigh frequency ultrasound mechanical wave into corresponding electricalsignals. These electrical signals are received through transmit-receiveswitch 210 and optionally multiplexed into the desired signal path. Theexemplary digital signal processor receives the electrical signals anddistributes them to the processing path.

In general, the pre-processor includes conventional processingcapabilities to receive and process ultrasound as with conventionalultrasound signals. The conventional processing capabilities may includeconventional components needed to receive, process, and store thecorresponding sensor data such as analog-to-digital (A/D) conversion. Inthe system of FIG. 9, for example, the received signals are transferredfrom the interface 201 through the switch 210 to a Doppler gain 217,analog filter 219, and Doppler analog-to-digital converter (ADC) 220where the signal is amplified, filtered, and digitized. Theamplification of the signal is controlled by a programmable gain DAC/POT222. The digital signal is then transmitted to a digital signalprocessing (DSP) chain on the FPGA 213. The exemplary system is a 16-bitdata system and has an internal clock speed of 135 MHz.

If sensors on the elongate body are optionally used to further detectECG activity, then appropriate electrocardiography components andprocessing capabilities are provided. The same is true for EEG signalprocessing, EMG signal processing, acoustic sensor processing, pressuresensor processing, optical sensor processing and the like. Referring toFIG. 9, a right shoulder 225 cooperates with an ECG lead 111. The ECGsignal is amplified, filtered, and otherwise modified by variouscomponents including ECG gain 219 and ECG analog-to-digital converter220. As is apparent from FIG. 9, the ECG signal processing is carriedout by separate components than the Doppler signal processing.

System 100 further includes other features such as a computer processor140 implementing the guidance and navigation processing techniquesdescribed herein and a digital-signal-processor 215 connected to atemperature sensor 227 for measuring and recording other systeminformation.

Unlike conventional systems, pre-processor 139 and processor 140 includeprogramming and processing capabilities to evaluate information fromintravenous signals obtained from the sensors to provide specificresults related to the guidance, positioning and confirmation oflocation as described herein. In general, the guidance system includesprogramming and capabilities of a pre-processor and processor adapted toextract information from the sensor signals based on desired parameters,evaluate the pre-processed information based on correlations and/orother information (e.g. knowledge of the phase of navigation), anddetermine a result related to the guidance, positioning and confirmationof location. Moreover, the system of the invention may be able to returna result based on in vivo non-image based ultrasound alone without theneed for X-rays verification.

The exemplary device is enabled to transmit and receive signals tocollect information for use in the navigation and placement process ofthe invention. In various embodiments, the device transmits anon-imaging ultrasound signal into the vasculature using a non-imagingultrasound transducer on the endovascular device. The device receives areflected ultrasound signal with the non-imaging ultrasound transducer.

In one aspect, the processor 140 is adapted and configured usingsoftware, firmware or other programming capabilities to receive andprocess physiological signals including, but not limited to, a venousblood flow direction, a venous blood flow velocity, a venous blood flowsignature pattern, a pressure signature pattern, A-mode information, anda preferential non-random direction of flow, as well as the capabilityto pre-process these signals to provide parameter features as inputs tothe processor. In various embodiments, the processor is optionallyadapted and configured to further receive and process other signals suchas an electrocardiogram signal, a P-wave pattern, a QRS-complex pattern,a T-wave pattern, an EEG signal, and an EMG signal. Further discussionof other signal information and parameters suitable for use with thesystem of the invention is provided below.

The exemplary processor provides an output related to the probableposition of or guidance information relating to the device within thevasculature. The exemplary processor contains, for example, rules,functions, or relationships used to determine the probable locationand/or movement of the device within the body. Various embodiments ofthe guidance system described herein apply mathematical analysis to thepre-processed inputs including, for example and without limitation,mathematical functions, moving windows, weights, adaptive weights,partitioning of a power spectrum, ratios of pre-processed inputs,iterations, updating of values, fuzzy logic, neural networks, membershipfunctions, features, inference rules, output, and feedback, alone or inany combination.

In general, the processing of the signal information to provide a resultto the output device generally includes the following operations. Thefirst step is to extract information related to one or more desiredparameters from the signal inputs (e.g. retrograde/antegrade power).Depending on the application, the information may be a numerical valuederived from the Doppler signal and optional other signals (e.g. ECGsignal).

Next, the processor receives the extracted information as inputs. Invarious embodiments, the processing of the input information involvesdetermining its degree of membership, or membership value, to a set ofpredefined input membership functions or classes for catheter tiplocation (e.g. push the catheter in, stop and keep the current tiplocation, pull back the catheter, etc.). When features cannot bedescribed as only a single membership function, a combined membershipfunction may be introduced. Next, the processor evaluates membershipvalues for the possible output membership functions. This may include,for example, applying a set of inference or IF-THEN rules in a fuzzylogic based algorithm, where if certain criteria are met, then aparticular zone or state is indicated. Alternatively, a neural networkbased algorithm can be used, as described herein. Next, the processorcalculates a score based on the membership functions and derives adefinite result related to the tip location. In various aspects,weighting is used in the final processing of the various parameters tosignify the relative impact of each and adapt the signal to the overallcondition of the data set. In various respects, the processor outputcorrelates to one of a number of predefined states. In some embodiments,a plurality of scores are generated or determined based on a pluralityof features, where the higher the score, the higher the probability orlikelihood of membership in a zone or state. In some embodiments, thehighest score of the plurality of scores is used to determine the stateor zone.

Finally, the processor output is translated into an indicator displayedon an output device. The indicator may be a unique light color, symbol,or other straightforward indication to a user.

With reference to FIGS. 1, 9, 10, and 11, the exemplary system 200includes processing features corresponding to the sensors of the system.The exemplary processing circuitry includes circuitry 202 for processingan in vivo non-image ultrasound signal and an optional circuitry 202 forprocessing an exemplary ECG signal.

In the exemplary embodiment, the optional ECG signal is used as aconfirmatory signal for the ultrasound signal processing. However, theguidance system and method disclosed may, and in many cases will,provide for sufficiently accurate guidance and positioning without useof a confirmation signal or other techniques for confirming position.Nonetheless, use of such other signals may be desirable for additionalplacement confidence, error reporting, or selective triggering of thedata acquisition and processing mechanism among other reasons.

In various embodiments, the Doppler-based processing and positioningtechnique includes the following operations explained with reference toFIG. 11. First, convert incoming signals from a time domain to afrequency domain, as described in steps 1105, 1110, 1115 and 1120.

At step 1105, get sampled Doppler data, antegrade and retrograde flow.

Next, at step 1110, filter antegrade and retrograde flow using a bandpass filter.

Next, at step 1115, in each data segment of antegrade and retrogradeflow, apply Hamming window (e.g. Hanning, Rectangular, Gaussian, etc.).

Next, at step 1120, calculate frequency spectrum (e.g. Fast FourierTransform, FFT) of each data segment.

Next, at step 1125, calculate power spectrum of antegrade and retrogradeDoppler data. Numerous different features are possible. ExemplaryDoppler features are further described, for example, in FIGS. 13, 14 and15.

Next, extract features for use in processor functions. For DopplerFeature 1a (DF1a), for example in step 1130, calculate the ratio ofretrograde/antegrade Doppler power in dB per heart beat, shown in FIG.13. For Doppler Feature 2 (DF2), for example in step 1135, calculatetotal Doppler power, as shown in FIG. 14. For Doppler Feature 3 (DF3),for example in step 1140, calculate dominant Doppler low frequencypower, as shown in FIG. 15.

Next, determine the output of each membership function using theinputted features, where the membership function provides informationregarding the location of the catheter tip based on a particular featureor features. Here, a feature includes all Doppler, ECG or other featureused by the system.

Next, assign a weight to each feature based upon zone score to becalculated, shown in FIG. 16. In addition or alternatively, applyweights to membership function determinations per membership class.

Next, calculate a score for each zone based upon Doppler or ECG feature,membership function, weight, and summation, shown in FIG. 16.

Next, check if there are any exceptions. If so, select exception result.

If there are no exceptions, the zone with highest score calculation ineach cycle determines which indicator to display, depending uponsubsequent time average.

The overall operation of the system will now be described with referenceto FIG. 16. FIG. 16 is a flow chart of the process flow used to inputsignals into a decision engine according to the methods and systemsdescribed herein. Based on the listing set out above, operations leadingup to the calculation of probability of membership function aregenerally performed by a pre-processor, generally designated 139.Operations including and after the membership function determinationstep are generally performed by the exemplary processor 140. One willappreciate, however, that the pre-processor and processor of theinvention may be modified depending on the application includingadapting the components to perform more or less operations and combiningall the operations into a single processing device.

In various embodiments, internal and external ECG signals are obtainedand fed into the pre-processor. The optional ECG signal pre-processingmay include a number of steps, such as:

1. Get a section of raw data from ECG signal train.

2. Detect QRS complex wave.

3. Detect the corresponding P wave.

4. Calculate the magnitude of P wave, P_mag, by peak detection.

5. Obtain the timing of each heart beat for Doppler (antegrade,retrograde) to align.

6. Calculate the P wave feature, pRatio, as follows:

-   -   Two P_mag: external P_mag and internal P_mag are calculated as        above, and pRatio is calculated as follows: pRatio=(internal        P_mag)/(external P_mag)

In general, the pRatio increases the catheter tip moves from theperiphery and towards the heart. Therefore, as the catheter tip isnavigated through the venous system, an increasing pRatio generallyindicates that the catheter is moving towards the heart and is moving inthe correct direction.

Since the P-wave in the internal ECG may elevate during the catheterinsertion, the P-wave in the external ECG may optionally be used as areference signal in the processing system. The reference value or acomparison to the reference value may be used as a feature as will bedescribed below. In addition, detection of a P-wave with biphasiccharacteristics can trigger an internal software flag that may be usedby the processor as a feature to determine the location status or zoneof the catheter tip. For example, in some embodiments, detection of abiphasic P-wave can indicate that the tip of the catheter has passed theSA node and has entered the right atrium, which in some applicationsindicates that the catheter tip has been advanced too far and should beretracted. Whether the P-wave is biphasic or not is another P-wavefeature.

By monitoring both the pRatio and whether the P-wave is biphasic or not,the catheter tip can be advanced towards the heart and towards thedesired destination, while also detecting whether the catheter tip hasbeen advanced past the destination.

Turning to FIGS. 9, 10, and 11, the exemplary system receives sampledsignal information from the one or more sensors as an input. FIG. 10illustrates the general flow of data within the system circuitry of FIG.9. FIG. 11 is a flow chart illustrating the flow of data for each datacycle.

The signal information from the sensors may consist of Doppler(ultrasound) signal, and optionally, other non-Doppler signals. In theexemplary embodiment, the system inputs include a Doppler signal, anintravascular ECG signal, and an extravascular ECG signal. The exemplarypre-processor algorithm includes sampling the Doppler signal at adesired frequency. In various embodiments, the frequency is betweenabout 20 to about 50 KHz/channel. The resulting sampled data may bestored in a memory, which may be local or off-device.

The signal input (sampled data) is passed through a series ofpre-processing functions to extract desired parameter information. Inthe illustrated example, when using optional ECG sensors, the signalsare first separated between a Doppler processing path and an ECGprocessing path. Next, the Doppler signal and ECG signals are subjectedto a number of processes to further extract desired parameterinformation.

In various respects, “parameter”, “criterion”, and “feature” are usedsomewhat interchangeably and refer to the desired information output bythe pre-processor and utilized by the processor as discussed below. Invarious respects, “parameter” refers to the information after theextraction and optional mathematical operations are performed by thepre-processor.

The pre-processing generally includes separating desired parameters fromthe sampled data. In one example, the device extracts Dopplerdirectional data (e.g. antegrade and retrograde or left and rightchannel). The data may be extracted at different memory locations if itis presented as a continuous incoming data stream from the sampler. Inthe illustrated example, each of the retrograde and antegrade signalsare subjected to a low pass filter, high pass filter, and spectrumanalysis to extract flow information in the retrograde and antegradedirections. The exemplary low pass filter removes noise associated withwall movement (low frequency). The high pass filter and spectrumanalysis separate the power spectrum data as shown in FIG. 11. The datais further subjected to other operations such as Hamming, fitting (e.g.to a Gaussian curve), and Fast Fourier Transformation (FFT) to focus ona specific parameter or feature of interest.

The exemplary pre-processing identifies at least one desired parameterin the data stream. In an exemplary embodiment, the pre-processoroutputs the following parameters to the processor: a ratio of theantegrade to retrograde flow, a difference between antegrade andretrograde flow velocity, Doppler signal total power, and a ratio ofaverage low velocity power to high velocity power.

The exemplary pre-processor also performs numerical calculations on theextracted information before transmitting to the processor. Thepre-processor operations may include adding, subtracting, combining(e.g. to provide a ratio), averaging, and more. As shown in FIG. 11 andfurther described in FIG. 13, for example, the pre-processor combinesthe extracted retrograde and antegrade power values to determine a ratioof retrograde/antegrade power corresponding to a desired “Dopplerfeature 1a.” Similarly, other mathematical operations are performed togenerate “Doppler feature 2” (the total Doppler power) as shown in FIG.11 and further described in FIG. 14. Similarly, “Doppler feature 3”(dominant low frequency power) is shown in FIG. 11 and further describedin FIG. 15.

Doppler Feature #1a: Ratio of Antegrade to Retrograde Doppler for bothhigh frequency and low frequency components (DF1a). Doppler Feature #1acan be used to determine whether the catheter tip is being advanced inthe right direction. In some embodiments, frequencies below 15000 Hz,14000 Hz, 12000 Hz, 11000 Hz, 10000 Hz, 9000 Hz, 8000 Hz, 7000 Hz, 6000Hz, 5000 Hz, 4500 Hz, 4000 Hz, 3500 Hz, 3000 Hz, 2500 Hz, 2000 Hz, 1500Hz, 1000 Hz or 500 Hz can be used with this feature. In someembodiments, frequencies above 15000 Hz, 14000 Hz, 12000 Hz, 11000 Hz,10000 Hz, 9000 Hz, 8000 Hz, 7000 Hz, 6000 Hz, 5000 Hz, 4500 Hz, 4000 Hz,3500 Hz, 3000 Hz, 2500 Hz, 2000 Hz, 1500 Hz 1000 Hz, 500 Hz or 0 Hz canbe used. In some embodiments, a frequency bandwidth between the highcutoff and the low cutoff can be used.

Doppler Feature #1b: Difference of Antegrade to Retrograde Doppler for abandwidth of frequencies (DF1b). Doppler Feature #1b can be used todetermine whether the catheter tip is being advanced in the rightdirection. In some embodiments, frequencies below 15000 Hz, 14000 Hz,12000 Hz, 11000 Hz, 10000 Hz, 9000 Hz, 8000 Hz, 7000 Hz, 6000 Hz, 5000Hz, 4500 Hz, 4000 Hz, 3500 Hz, 3000 Hz, 2500 Hz, 2000 Hz, 1500 Hz, 1000Hz or 500 Hz can be used with this feature. In some embodiments,frequencies above 15000 Hz, 14000 Hz, 12000 Hz, 11000 Hz, 10000 Hz, 9000Hz, 8000 Hz, 7000 Hz, 6000 Hz, 5000 Hz, 4500 Hz, 4000 Hz, 3500 Hz, 3000Hz, 2500 Hz, 2000 Hz, 1500 Hz, 1000 Hz, 500 Hz or 0 Hz can be used. Insome embodiments, a frequency bandwidth between the high cutoff and thelow cutoff can be used.

Doppler Feature #2: Ratio of Total Doppler Power to noise floor estimate(DF2). The Total Doppler Power is related to the total blood flow. Insome embodiments, frequencies below 20000 Hz, 19500 Hz, 19000 Hz, 18500Hz, 18000 Hz, 17500 Hz, 17000 Hz, 16500 Hz, 16000 Hz, 15500 Hz, 15000Hz, 14500 Hz, 14000 Hz, 13500 Hz, 13000 Hz, 12500 Hz, 12000 Hz, 11500Hz, 11000 Hz, 10500 Hz or 10000 Hz, and above 0 Hz, 20 Hz, 40 Hz, 60 Hz,80 Hz, 100 Hz, 120 Hz, 140 Hz, 160 Hz, 180 Hz, 200 Hz, 220 Hz, 240 Hz,260 Hz, 280 Hz, 300 Hz, 320 Hz, 340 Hz, 360 Hz, 380 Hz, 400 Hz, 420 Hz,440 Hz, 460 Hz, 480 Hz, 500 Hz, 600 Hz, 700 Hz, 800 Hz, 900 Hz or 1000Hz can be used.

Doppler Feature #3: Ratio of low frequency power to low frequency plushigh frequency power for both antegrade and retrograde Doppler (DF3).Doppler Feature #3 is related to the distance from the heart, and tendsto decrease in value as the catheter tip approaches the heart.Frequencies and frequency bandwidths that can be used include lowfrequency bandwidths, mid frequency bandwidths and high frequencybandwidths as described above.

Doppler Feature #4: Difference of antegrade to retrograde Doppler forbandwidth of frequencies. Exemplary frequency bandwidths include for usewith Doppler Feature #4 include the frequencies and frequency bandwidthsas described above.

The frequency cutoffs are based on correlations with blood flowvelocities. Low frequencies are associated with blood flow in theperipheral venous system, while high frequencies are associated withblood flow closer to the heart such as in the central venous system. Inaddition, where frequency bandwidths are used, a value or parameter canbe averaged over the frequency range encompassed by the frequencybandwidth.

Additionally or alternatively, a feature may be based on a segment, aportion or a signal in an electrocardiogram. One such feature is pRatio.This feature is a ratio of internal ECG P wave to external P wavereference value. Another such feature is RS amplitude (see FIG. 12B).Still another feature is the QRS complex. Still another feature isT-wave amplitude.

With regard to step 1130 in FIG. 11 and reference to FIG. 13, exemplaryDoppler feature 1a represents retrograde/antegrade power ratio (step1130). This feature is generated by calculating a moving average to thespectrum of antegrade and retrograde data previously extracted by thepre-processor (step 1131). The averaged value information is alignedwith a respective heart beat (step 1132) as shown, for example, in FIG.12A. Next in step 1133, the retrograde and antegrade power (dB) iscalculated for the heart beat and combined into a ratio.

Doppler feature 1b (DF1b) is generated using the same values as Dopplerfeature 1a (DF1a). While DF1a is a ratio, DF1b is generated by taking adifference of the antegrade and retrograde data. Although themathematical inputs are the same, the features are different.

With reference to FIG. 11 and in particular to FIG. 14, exemplaryDoppler feature 2 (DF2) is used to represent total Doppler power (step1135). This feature is generated by applying a moving average to theentire spectrum of flow data previously extracted by the pre-processor(step 1136). The averaged value information is aligned with a respectiveheart beat (step 1137) as shown, for example, in FIG. 12A. Next, thetotal power (dB) is determined for the heart beat (step 1138).

With reference to FIG. 11 and in particular to FIG. 15, exemplaryDoppler feature 3 (DF3) is used to represent Dominant Doppler lowfrequency. This feature is generated by applying a moving average to thespectrum of data flow previously extracted by the pre-processor andcalculating the low frequency power and high frequency power (step1141). The calculated power values are aligned with a respective heartbeat (step 1142) as shown, for example, in FIG. 12A. Next, the powervalues are combined into a ratio of low frequency power to low frequencyplus high frequency power to determine the dominant low frequency power(step 1143).

In other aspects, one or more features may be combined in a differentway or used as part of a different function or feature. In someembodiments, features can combine information related to multiple signalsources such as ECG, Doppler, and other sensors, such as oxygensaturation or carbon dioxide levels. In one specific aspect, one or morefeatures may be combined or compared in order to determine a weightratio. The weight ratio changes the importance of the Doppler signalcompared the other inputted signals in the processor. In one exemplaryembodiment, the weight ratio is a Doppler ECG CAJ weight ratio. Thisweight ratio is used to determine the significance of Doppler signalcompared to ECG, in particular when the instrument is advancing withinthe vena cava approaching the caval-atrial junction. When the ratio islarge, the processor places more emphasis on the information derivedfrom the Doppler signal. When the ratio is low, the processor placesmore weight on the ECG signal features. The weighting ratio isdetermined at every time step since conditions may change which mayaffect the quality of the Doppler and ECG signals. In one exemplaryembodiment, this ratio is based on Doppler Feature #2 and pRatio.

In various embodiments, the pre-processor extracts parameter informationfrom additional non-Doppler sensors after separation from the Dopplersignal. In an exemplary embodiment, the pre-processor processes an ECGsignal. In an exemplary embodiment, the device includes internal andexternal sensors for providing an intravascular ECG signal and external(outside the body) ECG signal. The ECG signal is passed through an ECGfront end, ECG filter, and PQRS peak detection element to extractinformation related to the PQRS peak. In an exemplary embodiment, thepre-processor outputs a correlation or ratio of the intravascular P-waveto the external P-wave as the desired ECG parameter. One will appreciatethat other ECG-based features may be extracted from the ECG waveform.Examples of other features that may be extracted and used by the systeminclude, but are not limited to, absolute peak values, average peakvalues, presence or absence of a peak, and time from peak-to-peak orbeat-to-beat. For example, the system may extract information related tothe RS peak, T-wave, S-wave, and more. The exemplary ECG parameter isoutput to the processor with the Doppler parameters above. In variousembodiments, the features extracted from the non-Doppler signal arecombined with the Doppler features as inputs in the pre-processingsoftware.

One will appreciate from the description herein that the system may makeuse of signal s other than, or in lieu of, Doppler and ECG. For example,the system may make use of sensors and data related to respiration,oxygen saturation, and more. The data used by the system may becollected in real-time. The data may be acquired from memory or anothersource. For example, information can be collected, stored, and usedlater, such as by performing an assay and using information related tothe assay later during navigation.

The software implementing the pre-processing techniques described can beapplied in different ways. In various embodiments, the software controlsare applied to the frequency domain after performing a Fast FourierTransform (FFT) or in the time domain (no FFT). A typical number ofpoints for the FFT are 512, 1024, 2048, and 4096. These numbersrepresent the length of a data vector. The signal can be averaged overtime or over the number of samples both in time and frequency domains.The on-line averaging uses a filter window of variable length (e.g.between 3 and 25 samples) to average along a data vector. Themulti-lines averaging computes the average of a selectable numbers ofdata vectors. The can spectral power can be computed in the frequencydomain from the shape of the power spectrum for each of the consideredsignals (e.g. directional Doppler). In an exemplary embodiment, thespectral power of the directional Doppler spectra is used todifferentiate between retrograde and antegrade blood flow.

Accordingly, the pre-processor receives signal information comprisinginformation from a variety of sensors, extracts desired parameterinformation in successive steps, and optionally performs a number ofcalculations on the extracted information. The pre-processor receivesthe complex signal information and outputs discrete desired parameters,in the exemplary case, Doppler features 1a, 1b, 2, and 3 and an ECGfeature. Thus, the signals are substantially transformed to obtain thedesired parameter information. Nonetheless, the parameter information isgenerally representative of the sensor signal environment.

Unlike conventional systems that merely digitize a sensor signal of asingle type (e.g. A/D conversion), one will appreciate from thedescription herein and the figures that the pre-processor of theinvention performs a significant amount of processing on signal data toprepare the data for processing by the processor. The pre-processor ofthe invention can also receive as an input signal data consisting of avariety of types of signals such as Doppler, ECG, and more. The systemof FIG. 9, for example, receives data from a Doppler sensor and ECGsensors and outputs information specifically related to antegrade power,retrograde power, total Doppler power, low frequency Doppler power, andECG PQRS peak.

As discussed above, the pre-processing entails a number of separationand extraction operations. Although the parameter information output bythe pre-processor reflects the signal input, and the sensor environment,the pre-processor outputs are directed to specific information of use bythe interrelated processor. One will appreciate that the pre-processormay be configured in various manners depending on the application toreceive, analyze, condition, and otherwise modify the incoming sensordata.

One will appreciate that the pre-processing may identify a variety oftypes of parameters. The pre-processing may extract single data points,data ranges or streams, and more. For example, the system may collectDoppler data over a segment of time, and the pre-processing may separatea segment of the Doppler data based on pattern recognition. Thepre-processed parameters may be quantitative or qualitative, binary orfuzzy. More information regarding the parameters suitable for use withthe device of the invention is provided below.

While described above with specific reference to Doppler and ECG, thetechniques for navigation within the body are not so limited. Thefeatures used as part of a guidance system as well as the membershipfunctions and adaptive weights applied to those functions may be alteredto provide guidance to other parts of the anatomy or utilize otherinputs/signals to determine location and/or position. Other signalsnaturally generated by the body such as electrical or acoustic signals,for example, may be utilized as part of a membership function.Additionally or alternatively, artificial signals (i.e. not generated byor within the body) may be introduced into, on, or about a region orlocation of the body and then utilized as part of a membership function.In still other alternatives, other instrumentation may be added to thecatheter described herein, or separate devices or instruments may beutilized to provide membership function information in addition toDoppler. Other devices or capabilities include, but are not limited to,other ultrasound modes, encoded signals, acoustic signals, magneticsignatures, and the like. These signals and devices may be introducedinto the body, detected, and then utilized in a membership function.

With continued reference to FIGS. 9, 10, and 11, the system 200 includesa processor for receiving the parameter information from thepre-processor as inputs. The processor is adapted and configured toprocess the input information and output a result related to theposition, movement, or confirmation of location of the sensor in thevasculature.

Both the exemplary pre-processor and processor within the system may beadapted and configured with software, firmware, or other programmingcapabilities to receive and process the features as described.

In contrast to the pre-processor, the processor generally conductshigher-level, more sophisticated processing of the respective data. Inpart, the processor implements algorithms and makes decisions whereasthe pre-processor generally extracts embedded information and performsbasic mathematical operations.

In various embodiments, the positioning method includes comparing theparameters to another value. In an exemplary embodiment, the processorcompares the flow energy directed away from the endovascular device tothe flow energy directed towards the endovascular device. In one aspect,the system selects for comparison the flow energy related to blood flowwithin the range of about 2 cm/sec to about 25 cm/sec.

In various embodiments, the positioning method includes processing thereflected ultrasound signal to detect indicia of pulsatile flow in theflow pattern. The indicia of pulsatile flow may be any of a number ofdifferent parameters. The indicia of pulsatile flow may be: a venousflow pattern, an arterial flow pattern, an atrial function of the heart,and the like.

In various embodiments, the pre-processor makes use of decisionprocessing. In various embodiments, the pre-processor separates adesired parameter from the signal data, makes a comparison, and thendecides whether to store information related to the parameter for usebased on the comparison.

In various embodiments, the pre-processor and/or processor includefilters. Selective filtering of certain frequencies may be used toremove undesired artifacts and frequency components, e.g., highfrequencies indicative of a high degree of turbulence. Selectivefiltering also may be used to emphasize certain frequencies as beingmore important in the decision making process. For example, the lowestand the highest relevant frequency of the spectrum (i.e. the lowest andthe highest relevant detected blood velocity) can be associated withcertain location in the vasculature and in the blood stream.

One will appreciate from the description herein that the device inaccordance with the invention may be modified to perform thepre-processing and processing functions within different structures. Forexample, some of the pre-processing may be performed on-board a sensor.Some or all of the pre-processing may be integrated into the processoror provided as a separate unit. In addition, the order of the operationsmay vary depending on the application.

The processor may be configured to process the parameter inputs byadapting processing techniques understood by one of skill in the artfrom the description herein. In various embodiments, the processorutilizes artificial intelligence programming. Examples of artificialintelligence programming that can make use of the principles describedherein include, but are not limited to, logic such as first order logic(e.g. fuzzy logic) and proposition logic, an expert system, a neuralnetwork, and an inference engine.

With continued reference to FIGS. 9 and 10, the processing platform 4can be a generic one like a personal computer or a dedicated onecontaining digital signal processors (DSP). The computing platformserves two purposes. It provides the processing capabilities of thepre-processor 139 and processor 140, which allows data processingalgorithms to run. The various data processing algorithms employed bythe various methods of embodiments of the current invention aredescribed in greater detail below. The other purpose of the computingplatform is to provide “back-end” functionality to the system 100including a graphical user interface, data storage, archiving andretrieval, and interfaces to other systems, e.g., printers, optionalmonitors, loudspeakers, networks, etc. Such interfaces can be connectedin a wired or wireless configuration. Those of ordinary skill willappreciate that the conventional components, their configurations, theirinteroperability and their functionality may be modified to provide thesignal processing and data capabilities of the guidance system 100.

Guidance and Positioning Principles

While desiring not to be bound by theory, certain aspects of theinvention operate based on the principle that certain locations in thevasculature can be identified by specific blood flow parameters andcorrelation between these blood flow patterns at those locations. Thesepatterns may be based on, for example, Doppler blood flow measurements.This information may be supplemented and/or confirmed based onparameters related to other sources such as an intravascular and/orextravascular electrocardiogram and blood pressure. Moreover, thedirection of travel for a sensor-equipped endovascular device relativeto the direction of blood flow can be derived from Doppler information.In various respects the methods and systems for intravascular guidanceand placement are based on the recognition of patterns in the signalsfor different physiological parameters and correlation of those signalpatterns.

Signals or information based on one or more of the above may be used bythe pre-processor and input to the processor described herein toaccurately determine a position. Alternatively, one or more principlesand rules used by the processor system may be based on one or more ofthe above.

In various aspects of the invention, the system processes positionand/or direction information in real-time using the sensors, techniques,data acquisition, and processing described herein. In the case of aPeripheral Inserted Central Catheter (PICC) line, a user receivesreal-time, constant feedback on advancing a guided vascular accessdevice to allow the PICC to advance along a desired path from aninsertion vein into the vena cava and towards the sinoatrial node. Thesystem recognizes unintended entry into other veins based on thedifferences in flow patterns or other parameters extracted from theintravascularly placed sensor signals. As such, the system may recognizeunintended entry into the right atrium, inferior vena cava, jugularvein, the subclavian vein. Additionally, the system may detect when asensor is against the vessel wall. By monitoring and processing the dataacquired from sensors positioned on the endovascular access device, theuser can be notified when the device tip reaches the ideal placement inthe lower third of the superior vena cava, at the caval-atrial junction(CAJ) and/or in the proximity of the sinoatrial node. The systemrecognizes these locations of the vena cava, and other vascularcomponents, by analyzing sensor-acquired data to identify unique flowpatterns in order to confirm placement, location and/or guidance.

In various embodiments, the sensor technology described herein is only anon-imaging ultrasound. The unique flow patterns may be discerned usingnon-imaging ultrasound and as such does not require all the elementsthat make ultrasound imaging possible, such as scanning with a movingtransducer, working with phased arrays and beam forming, and the like.As such, embodiments of the present invention provide a vascular accessand guidance system with a hand-held, simple, inexpensive userinterface. Non-imaging ultrasound includes a number of variousultrasound techniques and processing configurations, by way ofnon-limiting example: A-beam ultrasound, Doppler ultrasound, continuouswave Doppler ultrasound, pulsed Doppler ultrasound, color Dopplerultrasound, power Doppler ultrasound, bi-directional Doppler ultrasound,and ultrasound techniques that provide for the determination of velocityprofile based on correlation of blood flow and time.

The physiological information is analyzed in order to identify thelocation in the vasculature where the information was acquired. Becausebody functions are unique at certain corresponding unique locations inthe vasculature, embodiments of the present invention can usemeasurements of the body functions and detect location in the body.

In various embodiments, the present invention relates to the use of theblood flow profile to detect the proximity of the sinoatrial node and ofthe caval-atrial junction. FIG. 20 illustrates the anatomical locationof the caval-atrial junction at the confluence between the superior venacava (SVC) and inferior vena cava (IVC) just before entering the rightatrium (RA). FIG. 21 illustrates the anatomical location of thesinoatrial node at the caval-atrial junction (CAJ). The function of thevasculature and the function of the heart are unique at the caval-atrialjunction both in terms of blood flow profile and of electrical activityof the heart.

In various embodiments, the methods, devices and systems describedherein use a “multi-vector” or “multi-parameter” approach. Multi-vectorapproach refers to the use of multiple parameters such as the blood flowinformation, the electrical activity information, and the relationshipbetween the two.

In various embodiments, the system is a multi-parameter system that usesintravascular electrocardiograms or other physiological ornon-physiological sensor data in combination with the ultrasound signal.In various embodiments, the system according to the present inventionidentifies the blood flow profile characteristic of the caval-atrialjunction and optionally identifies ECG waveform patterns characteristicof the proximity of the sinoatrial node. When both these patterns arepresent, the system indicates to the user that the desired targetlocation has been reached. One benefit of this approach is that thelocation is accurate without the need for ECG signals and other methods.Another benefit of the exemplary approach using ECG as an optionalconfirmatory signal is that the blood flow and the electrical activityare independent physiological parameters and thus, by considering themtogether, the accuracy of the location information is further improvedover any system dependent on ECG signals alone.

With particular reference to FIGS. 9, 10, and 16, the operation of theprocessor 140 will now be described in greater detail. As shown in FIG.10, the processor receives the pre-processor outputs, processes thedata, and provides a result 250 related to navigation and guidance ofthe sensor. The exemplary processor 140 sorts the parameter informationfrom the pre-processor into membership functions.

As discussed above, the pre-processor 139 extracts and translates sensorsignals into processing parameters. The processing parameters(variables) output by the illustrated pre-processor are shown in Table 1below.

TABLE 1 Processing Variables Feature Parameter/Variable Doppler 1a(DF1a) Ratio: antegrade flow to retrograde flow Doppler 1b (DF1b)Antegrade flow minus retrograde flow Doppler 2 (DF2) Doppler SignalTotal Power Doppler 3 (DF3) Ratio: Low Velocity power to (low frequencypower plus high frequency power) ECG 1 (E1) Ratio: P wave intravascularto P wave external

The first four parameters—DF1a, DF1b, DF2, and DF3—relate to a Dopplersignal. The processor also optionally receives a non-Doppler signal, E1.In one aspect, the non-Doppler signal is based on one or more portionsof an electrocardiogram signal as described herein. The variables aregenerated by the pre-processor as explained above. The methods ofextracting the parameters from the sensor signal are described abovewith respect to FIGS. 13-15.

The non-Doppler signal may be used for several purposes. For example,the non-Doppler signal can be used to align the Doppler parametersand/or sampling with physiological events (e.g. a heartbeat, inhalationof the lungs, or a nerve signal).

In various embodiments, the processing is carried out by recognizingflow patterns and/or signatures in the blood flow. In variousembodiments, the processor compares a respective processor input(pre-processor output) to a calculated or expected value. In variousembodiments, the processor compares a respective processor input tovalues in a look-up table. The use of a look-up table provides theadvantage of reducing the number and complexity of processing operationsthat must be performed. In various embodiments, the processing makes useof thresholds. For example, an increase of a feature value above athreshold may indicate the catheter tip is in a specific zone orlocation.

The processor may make use of a computer platform programmed withsoftware or embedded with code to perform the processing functionsdescribed herein. In various embodiments, the system utilizes standardintravascular system components and a computer program product forperforming instructions related to the functions described herein.

In the exemplary case, the software is based on artificial intelligence.In various embodiments, the processor operates based on fuzzy logic. Theprinciples and techniques for utilizing fuzzy logic systems aredescribed in the following: European Patent Application No. 97830611.6filed on Nov. 18, 1997 entitled “FUZZY LOGIC METHOD FOR AN INDIRECTMEASURE OF A PHYSICAL SIGNAL TO BE MONITORED, AND CORRESPONDINGMEASURING DEVICE” with Publication No. EP 0917069; Application No.08/938,480 filed on Sep. 30, 1997 entitled “FUZZY LOGIC TISSUE FLOWDETERMINATION SYSTEM” granted as U.S. Pat. No. 5,857,973; ApplicationNo. PCT/US01/09115 filed on Mar. 22, 2001 entitled “METHOD AND APPARATUSFOR ASSESSING HEMODYNAMIC PARAMETERS AND BLOOD VESSEL LOCATION WITHINTHE CIRCULATORY SYSTEM OF A LIVING SUBJECT” with InternationalPublication No. WO 01/70303; application Ser. No. 10/961,709 filed onOct. 7, 2004 entitled “ULTRASOUND IMAGING SYSTEM PARAMETER OPTIMIZATIONVIA FUZZY LOGIC with U.S. Patent Application Publication No.2006/0079778; and application Ser. No. 10/329,129 filed on Dec. 24, 2002entitled “METHOD AND APPARATUS FOR WAVEFORM ASSESSMENT” granted as U.S.Pat. No. 7,043,293, each of which is incorporated by reference in itsentirety.

Time Intervals and Selective Acquisition and Processing

Time underlies much of the data acquisition and processing methoddescribed herein. For example, the time of acquisition, samplingfrequency and PRF, and other time factors play roles in the describedpositioning method.

In various embodiments, increasing sampling frequency (i.e. PRF) mayincrease resolution of the system. With reference to FIG. 12A,increasing the sampling frequency may increase the number of data pointsfor each processing cycle between a start time, t0, and stop time, tf.

In various embodiments, the position and guidance of the sensor isbroken into discrete movement increments and the sampling frequency isfaster than the sensor is expected to move. Put another way, thesampling frequency may be tied to other factors than mere movement ofthe sensor such as the heart rate, breathing rate, and more. As thesensor moves from a location S0 to location S1, the processing systemreceives more than one data set. In other cases, signal data from morethan one period or point of time may be bundled together.

Additionally, by analyzing the behavior of a parameter over a period oftime, the system can realize several advantageous features. FIG. 12Aillustrates an exemplary period of time selected by the system foranalysis, which will generally be referred to here as the “processingwindow.” The window starts at time t0 and ends at time tf.

In various embodiments, the processing windows for all or a portion ofthe positioning procedure are of substantially uniform length in thetime domain. In various embodiments, the processing windows are shorterfor increased granularity in one region than another. For example, itmay be desirable to sample data faster and increase the rate ofpositioning analyses as the sensor approaches a desired or undesireddestination. By segmenting the signal data and modifying the frequencyand length of the segments, the speed and performance of the system mayalso be improved or adjusted. In various embodiments, the systemrecognizes when the signal data in one block of time is substantiallysimilar to another and either bypasses the processing operation ordeletes the subsequent block as being redundant.

Signal pre-processing and processing functions on any or all of thecollected signals can be performed over time intervals. In one specificexample where the signals are derived from ECG and Doppler signals, oneor more time intervals could be selected to include correlation betweenthe ECG and Doppler signals within a sub-interval of a heartbeat (shown,e.g., in FIG. 12A). Exemplary waves, points, intervals and subintervalsfor the heart rhythm that may be used for correlation measurements,pre-processing or processing functions include, for example, (a) any ofthe various waves or portions thereof such as P-wave, Q-wave, R-wave,S-wave, T-wave, or U-wave; (b) any of the various segments or portionsthereof including the PR segment or ST segment; (c) any of the variousintervals or portions thereof including the PR interval, the QRSinterval, the QT interval, the ST interval; (d) the amplitude of anyportion of the ECG waveform such as the P-wave amplitude, RS amplitude,T-wave amplitude; and (e) the use of the overall shape, amplitude orvariation in a portion or sub-portion of the signal such as the QRScomplex, the J point or any other inflection point in theelectrocardiogram,

Features that may be obtained from pre-processing operations includeenergy and waveforms of the ECG signals such as QRS complex ratios andantegrade and retrograde blood flow velocity signals. Features providedby collected signal pre-processing over the same time interval or atdifferent time intervals (i.e. in synchrony with a specific portion ofthe QRS complex, respiratory cycle or other timing sequence imposed onthe data collection and pre-processing activities) are utilized inmembership functions and other aspects of the processing describedherein. These optional features include, but are not limited to, ECGsignal waveform, amplitude, position or other information related to theP-wave, QRS complex and the T-wave.

FIG. 12A illustrates a standard ECG wave. The ECG can be broken downinto three primary components: the P-wave, QRS complex, and T-wave.These different components along with numerous other segments and valuesare indicated on FIG. 12A. Each of the different waves corresponds todifferent electrical activities of a normal heart. The P-wave may be ofinterest because it corresponds to atrial depolarization. As isunderstood in the art, the P-wave becomes distorted during atrialfibrillation. As the above illustrates, even in the case of patientswith atrial fibrillation, the atrial electrical activity, which may notbe seen on the regular skin ECG, becomes visible and relevant as theintravascular ECG sensor approaches the caval-atrial junction. Both theamplitude of the atrial electrical activity and its relative amplitudeversus the QRS and R-waves change visibly at the caval-atrial junctionin the close proximity of the sino-atrial node.

In addition to P-wave changes, various other portions of the QRS complexmay be used with the positioning techniques described herein. Forexample, the amplitude of one or more segments may be compared to anyportion of or all of an external ECG signal, an internal ECG signal or areference ECG signal. In another alternative aspect, an ECG signal maybe compared beat-to-beat or compared against earlier obtained ECG data.In one specific aspect, the amplitude of a portion or a segment of theelectrocardiogram is used in the positioning process. In one alternativeembodiment, the relative amplitude of a portion of the QRS complex isused. In one specific embodiment illustrated in FIG. 12B, the amplitudeof the RS signal is used. FIG. 12B illustrates an exemplary ECG waveformfrom the brachial area (left side of the figure) and from thecaval-atrial junction or CAJ area (right hand side of the figure). Inthis illustrative embodiment, the RS amplitude is compared against priormeasured RS amplitude. FIG. 12B illustrates how the overall RS amplitudeincreases when advancing towards the CAJ from the brachial area. Thisinformation may be used in conjunction with positioning techniquesdescribed herein. For example, when a comparison of prior RS amplitudesignals reveals that the amplitude has increased and remainedconsistently increased, then the processing algorithm may use thatinformation as an additional factor for determining position of theinstrument.

FIG. 12B illustrates one exemplary use of changes in amplitude of aportion of the electrocardiogram signal. Other portions of theelectrocardiogram signal may also be used in a similar fashion dependingupon the particular patient circumstances. Consider for example the caseof a patient experiencing an irregular heart rhythm during a catheterplacement procedure. In that event, the processing system may stop usingone portion of the electrocardiogram made unreliable by the irregularrhythm and instead analyze a different portion of the electrocardiogramsignal that is believed reliable. In addition or alternatively, thesystem may alter the weighting factor applied to those portions of theprocessing system that relies on the electrocardiogram information. Byadjusting the weighting factor of the now unreliable ECG information,the processing system adapts to the reliability of ECG information.

In various embodiments, one or more parameters may be related to oraligned with Doppler signal information at a specific moment in theheart cycle. A parameter or feature that is aligned includes an averagevalue, a summation, a truth value (e.g. has it passed a thresholdvalue), a maximum value or a minimum value, and the like. As shown inFIG. 12A, for example, the data point or data period for the parametersmay be selected based on the desired physiological event, in this casethe heart pumping. This alignment may also occur by selecting the sameportion of the electrocardiogram cycle for successive heartbeats. Theportion of the electrocardiogram used to correlate the various signalsused by the system during either or both of pre-processing and positioncalculations may be any of those electrocardiogram signal indications(i.e., waves, segments, intervals, points or portions) illustrated ordescribed herein or with respect to FIGS. 12A and 12B. By example inreference to FIG. 12A, one feature may incorporate parameters obtainedduring times t1 (i.e., R-wave peak), t2 (i.e., S-wave peak), or both. Inone specific example, Doppler feature 3 may incorporate a parameteranalyzed over a period t3 (i.e., a time period corresponding to theinterval from the S-wave to the J point). In the case of t3, anotherDoppler feature may be an average value, a summation, a truth value(e.g. has it passed a threshold value), a maximum or minimum, and thelike.

Each of the exemplary features DF1 (DF1a or DF1b), DF2, and DF3 are usedin combination in the analysis cycle shown in FIG. 11. When the sensormoves and/or new sample data is acquired, the cycle repeats and new DF1,DF2, and DF3 values are acquired. One will appreciate, however, that inthe next cycle DF1, DF2, and DF3 will likely be acquired at slightlydifferent times between t0 and tf and relative to each other.Alternatively, one or more of the features may be acquired at set timesrelative to t0, tf, or other indicia.

One will appreciate that, the feature values likely will vary whenshifted to different times within a single processing window (in thisexample corresponding to the ECG waveform). As will be understood fromthe description herein, the feature values may be aligned with specificevents. As described herein, features and parameters can be combined ina function or algorithm that relates the features to the parameters inorder to determine a score that indicates positional informationregarding the catheter tip.

In various embodiments, the properties of the ultrasound beam generatedby the sensor are modified with respect to time. For example, it may bedesirable to modify the operating frequency and/or the pulse repetitionfrequency to sample different target volumes or at different depths ofpenetration. The volume of the target of interest is defined as thethree-dimensional region encompassed by the beam geometry and containedin the acquisition (processing) window. In various embodiments, theoperating frequency is about 10 MHz to allow for a maximum penetrationdepth of about 20 mm. In various embodiments, the pulse repetitionfrequency (PRF) is about 40 kHz to allow the ultrasound wave topenetrate to a sufficient depth between pulses.

The modification of the processing based on the time function may beused to realize several unexpected advantages. For example, the periodof time for inspection can be used as a quasi-filter by narrowing theanalysis window to exclude undesirable data.

Aspects of the systems and methods described herein enable vascularnavigation and device positioning in patients having irregularheartbeats such as arrhythmia including, for example, atrialfibrillation. If an irregular heart rate is detected or indicated, theprocessing system may apply a weighting function to a period of timeover a specific portion of the ECG signal (e.g. the P-wave) during thesignal processing and/or pre-processing. As a result, the featureproduced from an irregular ECG signal may be weighted to reduce relianceon the ECG signal if the irregular aspect of the heart beat renders itunusable. If the irregular aspect of the heart beat, however, onlyrenders a portion of the ECG signal unreliable, then the pre-processingmay then be used to filter out the unreliable portion of the ECG signal.Alternatively, the irregular aspect of the heart beat may simply cause adifferent aspect of the ECG signal to be used based on the type ofirregularity presented by the patient. Thus, in a patient suffering fromarrhythmia, a ECG signal value may be different from a “normal” patientbut still usable in the arrhythmic patient. As such, the signalcollection and pre-processing features may be adjusted to utilizedifferent portions of the ECG signal based on the type of arrhythmia.

Any of a wide variety of physiological characteristics of the body maybe collected, pre-processed and then used with the pre-processor andprocessor to determine the location of the device within the body.Physiological characteristics often change depending upon location,relative movement, or proximity to structures within the body.

The signals used in the system described herein may be naturallyproduced by body functions, such as from electrical signals of the bodylike ECG, EMG or EEG. In addition or alternatively, the signal may bethe result of an interaction with the body from an artificial signal orsource introduced into a portion of the body. Such artificial signalsinclude those generated through use of ultrasound, magnetic, or electricfields (e.g. through contact with the body with a probe, electrode orinstrument in order to produce a signal or input at a specific,predetermined location in the body).

In various embodiments, one or both of the pre-processor and processormakes use of information related to the behavior in time of any of theparameters described herein. In one example, the behavior refers to thedifference between strongly pulsatile flows present in the right atrium,in the heart in general, and/or in the arterial flow compared to the lowpulsatility characteristic of venous flow. As the sensor moves, thepulsatile nature of the flow changes and the system makes adetermination based on this behavioral change or pattern. The system mayalso take into account a periodic change in behavior of the flowprofiles in comparison to the heart rate. In one example, a strongerperiodic change with the heart rate or pulsatility may be indicative ofthe right-atrial activity.

In various embodiments, the sensor, pre-processor, and/or processor aresynchronized for data acquisition and processing. The signal data can beprovided as data points triggered by activation of the sensor and/orrecording of a specific point in time in the data stream. The method ofthe invention may also use averaging, smoothing, and other techniques inconnection with processing of the real-time data.

Focusing on FIG. 12 a, the parameters output by the pre-processor mayrelate to the same point in time or different points in time within thesame processing window. Referring to FIG. 12 a, for example, oneparameter may correspond to t1 and another parameter used in the sameprocessing cycle may correspond to t2. In various embodiments, thesystem is configured to process the signal information overpredetermined periods of time such as t3. The predetermined periods maybe preset or may be modified by a feedback loop at the end of eachanalysis cycle.

The processing methods and algorithms may also identify important orunique signatures useful in guidance, localization or correlation. Themethod may include different or customized software or programming forprocessing ultrasound signal and/or other optional signal information.The processing may include processing of reflected ultrasound signal toidentify the caval-atrial junction or to determine the highest averagevelocity of a velocity profile.

Certain of the parameters used by the system may be more reliable ormore significant at different points in time. The system may make use ofthis fact. For example, if the antegrade flow velocity may be moresignificant during the strongest part of the contraction period, thesystem can analyze the antegrade flow velocity parameter only at thistime. Other parameters may be more significant over selected periods oftime than as specific periods. Yet other parameters may be moresignificant at peaks and valleys. Accordingly, the system may employfilters, synchronization of the sampling, recording, and processingfunctions, and other techniques to improve the parameter data to theprocessor. In various embodiments, the system weights the influence ofeach of the parameters. The system may employ an expert system such thatthe weights are changed based on expert knowledge. In variousembodiments, the weights can fluctuate between zero and one such that aparameter can have no influence, complete influence, or anything inbetween.

In various embodiments, another sensor and signal data are provided andconfigured as a trigger to acquire and/or process the ultrasoundinformation. In one aspect, the signal from one sensor is the triggerfor acquisition or processing of a signal from another sensor. In thismanner, the data from two different physiologic sensors may becorrelated in time and to the trigger signal. Alternatively, rather thantriggering acquisition data from the triggered sensor, all sensor datacould be collected and/or stored and the trigger could instead result inthe processing of only the subset of the data based on the trigger data.In either triggering scheme, the trigger sensor data and the triggeredsensor data are processed together to yield the benefits describedbelow. One will appreciate that the triggering method described may beused to correlate the data acquisition to the points in time whenparticular parameters are more or less significant.

In various embodiments, the optional intravascular electrocardiograph(ECG) signal is used for selective (gated) acquisition and processing ofthe blood flow information, depending upon the specific characteristicsof the electrocardiogram signal being utilized. For example, when theelectrocardiogram signal is produced by the heart, the gatingacquisition may be based on one or more integrals of the heart cycle. Inthis example, detection of the P-wave detection from anelectrocardiogram sensor may be triggering signal for acquiringultrasound data from an ultrasound sensor. As described herein, theunique P-wave signal detected when an electrocardiogram lead ispositioned in the superior vena cava near the sino-atrial node 8 can beused to confirm the detection of the unique blood flow pattern that alsooccurs in this area of the vasculature. In this way, the existence ofboth unique physiological signals from two different physiologicalsystems increases the accuracy of the guidance system embodimentsdescribed herein. This selective approach may increase the accuracy ofdetermining blood flow patterns corresponding to locations in thevasculature.

In various embodiments, a feature may be derived from a Doppler signalwaveform, amplitude, position, or other aspect. In various embodiments,the selective acquisition and processing is based on muscular orphysiological events such as those corresponding to:

-   -   1. Retrograde flow from atrial contraction;    -   2. Antegrade flow during systole, tricuspid valve closure and/or        atrium fill    -   3. Retrograde flow at end of systole, capacitance of atrium goes        to zero and negative pressure wave reverses flow in superior        vena cava, and    -   4. Antegrade flow during diastole, filling of both atrium and        ventricle

In various embodiments, the selective acquisition and processing aretriggered by acoustic signals from the body such as valve closing orfilling of a passage.

In various embodiments, the method of positioning an endovascular devicein the vasculature of a body includes processing the reflectedultrasound signal to detect indicia of pulsatile flow in the flowpattern. The indicia of pulsatile flow may be any of a number ofdifferent features. The indicia of pulsatile flow may be: a venous flowpattern; an arterial flow pattern or an atrial function of the heart.Likewise, the processing may be based on indicia of other events orfeatures.

Input Features for Navigation and Guidance

The above description provides a better understanding of thepre-processor outputs and nature and quality of the feature informationutilized by the processor. Although the exemplary system is described interms of three specific Doppler parameters, DF1a, DF1b, DF2, and DF3,and one ECG signal, E1, one will appreciate that a variety of featuresmay be used in accordance with the invention.

As described above, the pre-processor may be configured to extract andtransmit a number of feature values to the processor. The featureinformation will now be described in greater detail.

In various embodiments, the pre-processor is configured to receive asignal from the non-imaging ultrasound transducer and extract a featureincluding, but not limited to, a venous blood flow direction, a venousblood flow velocity, a venous blood flow signature pattern, a pressuresignature pattern, A-mode information, a preferential non-randomdirection of flow, and others.

Additional features useful in assessing location in the vasculaturebased on Doppler information are described below. Examples of some ofthe other features that can be used to determine sensor location in thevasculature from the blood flow velocity profiles include, but are notlimited to: a) comparing energy (e.g. as measured by spectral power infrequency domain) of each of the directions of bidirectional flow; b)bidirectional flow patterns in lower velocity range to detect thecaval-atrial junction; c) pulsatility to detect atrial activity; and d)the highest meaningful average velocity of the velocity profile andothers described herein.

In another example, one feature used for correlating the Dopplerfrequency (velocity) distributions to the anatomical locations relatesto the spectral power or the area under a specific Doppler frequencycurve (the integral computed of the frequency spectrum) in conjunctionwith the uniformity of differences in frequencies over the entirefrequency range. The sensor may be positioned in the superior vena cavalooking towards the heart and with the main blood flow stream movingaway from the sensor towards the heart. Based on the Doppler frequencycurves (e.g. the relative areas under each curve correlated to therelative amount of flow) over the whole range of Doppler frequencies(velocities), the system can make a determination, for example, thecatheter tip has been pushed into the jugular vein. Consequently, if theblood velocity profile shows larger spectral power in one direction itcan be inferred that this is the predominant direction of flow of theblood stream.

Another feature is related to the distribution of the low velocities intwo directions—towards and away from the sensor. In a vein, the bloodvelocities are different than in the right atrium. Therefore, most ofthe relevant spectral energy will be present in the low velocity range.Typically, low blood flow velocity range is from 2 cm/sec to 25 cm/sec.

Another feature is the similarity between the antegrade velocity curveand the retrograde velocity curve. At the caval-atrial junction (shownin FIG. 19) the curves are almost identical with similar areas (similarenergy or the area under curves) and with similar velocity distributions(similar velocity profiles or shape of the curves). This is indicativeof the similar inferior vena cava (IVC) and superior vena cava (SVC)flow streams joining together from opposite directions when entering theright atrium.

Another feature is the amplitude of the antegrade and retrogradevelocity curves. The higher the amplitude at a certain frequency, thehigher the signal energy (i.e. the more blood flows at the velocitycorresponding to that particular frequency).

Another feature is the amplitude of the highest useful velocitycontained in the antegrade and retrograde velocity profiles. In oneexample, useful velocity is defined as one being at least 3 dB above thenoise floor and showing at least 3 dB of separation between directions.The highest useful velocity may be an indication of the highest averagevelocity of the blood stream because the exemplary device intends tomeasure volumetric (average) velocities.

The correlation between the shape, amplitude, and other characteristicsof the intravascular waveforms and relative changes can also be used asthe feature information for positioning, guiding, or confirming sensorlocation in accordance with the invention.

As described above, the system may also make use of non-Dopplerinformation for different purposes, including, but not limited to,confirmation and error reporting.

Membership Functions

Turning back to FIGS. 10 and 16, the processing operation in accordancewith the invention will now be described in greater detail. As shown inFIG. 16, the Doppler signal and other optional signals are input to thepre-processor 139 where they are separated. The pre-processor outputsthe desired feature information and transmits the feature information tothe processor 140.

Various aspects of the system are based on the recognition of patternsin the sensor signals for different physiological features andcorrelation of those signal patterns. The pre-processor extractedinformation relates to the different, desired physiological features,and the processor identifies patterns and correlations among thepre-processed information.

Various aspects of the system and method of the invention correlate thefeatures to the phase of intravascular navigation. For purposes ofillustration, one example of the system and method in accordance withthe invention will be described with reference to FIG. 16.

Referring to FIG. 16, the exemplary processor sorts each of the Dopplerfeatures into membership functions 230 (also shown in Table 3 below).Given each feature value (shown in Table 1 above), the membershipfunction value, similar to a conventional probability function, iscalculated for each zone. The achieved purpose of the exemplary systemis to indicate the position of the catheter tip with plus or minus about3 cm, 2 cm, or 1 cm accuracy at the cavial atrial junction of the humanheart.

Various aspects of the system and method of the invention correlate theparameters to the phase of intravascular navigation. To that end, theprocessor utilizes inference rules governing the use of parameterinformation in the various “states” of navigation. The rules andprinciples used with the present navigation technique will be understoodfrom the description herein.

In order to determine the probable location of or recommended movementof the device, the exemplary guidance system utilizes the features ofDoppler signals in each state. The exemplary system uses an optional ECGsignal to increase the confidence level. Table 2 briefly describes therules governing the use of features in each state.

The exemplary states of navigation include state 0 (weak or lowusefulness of the parameter), state 1 (ECG P-wave is not elevated),state 2 (ECG P-wave is elevated), and state 3 (ECG signal is notelevated or ECG P-wave is elevated, and ECG p wave shows biphasic).

The states illustrated in Table 2 are based on known information aboutthe behavior of the Doppler parameter and optional ECG parameter invarious states or phases of navigation. For example, as is generallyunderstood in the art, the flow will generally flip from predominantlyantegrade to retrograde if the sensor improperly enters the atrium.Thus, the exemplary state 3 corresponds to predominating of theretrograde flow.

Additionally, the processor may take into account previous locationinformation. For example, state 3 may only be achieved after passingthrough one or more of states 0, 1, and 2. State 3 would only beexpected to be reached after the device is properly positioned in andnavigates the venous vasculature.

The exemplary system also makes use of the ECG signal for confirmationof location. In state 3, the ECG signal is expected to be low or theP-wave is elevated, and ECG P-wave shows biphasic. Thus, the states ofTable 2 incorporate known information about the environment of specificstates of navigation and current and prior navigation.

TABLE 2 The features of each state System output Clinical displayed onoperator's Doppler State ECG signal console Description action signalState 0 Weak or low usefulness

(Yellow) The Doppler signal is too weak, or any other unknown scenarioWait for about 5~10 sec, or push in/push out the catheter, and see ifthe sign changes Doppler power is relatively weak State 1 ECG p wave isnot elevated

(Green) The optimal location is ahead Advance the catheter Antegradeflow is dominant over retrograde flow State 2 ECG p wave is elevated

(Blue Bull's Eye) The catheter tip location is at the optimal locationStop and keep the tip location in the area, ready to wrap up theprocedure Dominant low frequency in both antegrade and retrograde flowState 3 ECG signal is not elevated or ECG p wave is elevated, and ECG pwave shows biphasic

(Red) Either the tip location is too deep in atrium or in wrong places,such as subclavin, azygos, IJ, or the stylet is coiled Pull back thecatheter until red sign changes to other signs Retrograde flow isdominant over antegrade flow

With continued reference to FIG. 16, next exemplary processor 140translates the parameter features (e.g. DF1 (DF1a, DF1b), DF2, DF3, andE1) from the pre-processor into membership functions 230 for furtherprocessing of the probability that the device is in or not in aparticular state of navigation. Table 3 illustrates the membershipfunctions. For a feature DF1, for example, the membership functions arePZ0D1, PZ1D1, PZ2D1, and PZ3D1. These membership functions correspond tothe parameter value in each of zones 0, 1, 2, and 3, respectively.

TABLE 3 Membership Functions Membership Function Feature PZ0D1 DF1 PZ1D1DF1 PZ2D1 DF1 PZ3D1 DF1 PZ0D2 DF2 PZ1D2 DF2 PZ2D2 DF2 PZ3D2 DF2 PZ0D3DF3 PZ1D3 DF3 PZ2D3 DF3 PZ3D3 DF3 PZ0E1 EF1 PZ1E1 EF1 PZ2E1 EF1 PZ3E1EF1

In general, the exemplary processor calculates a membership score foreach state of navigation (shown in Table 5 below) based on a specificset of rules to calculate the state with the highest probability (whichcorresponds to the result). The exemplary system makes use of the rulesdescribed in Table 2 above.

Table 4 lists the weighting matrix for each of the Doppler parameters ineach of the states of function. Thus, as shown in Table 4 and FIG. 16,for example, DF2 will be weighted by a factor of Wy3 in state 0. Instate 1, the weighting will change to Wg3.

The rules governing the use of the parameter information in the various“states” of navigation described herein inform the weighting of thecalculation and balancing of the contribution of the various parameters.The weighting is determined based on the contribution of eachparameter/feature to each class.

Additionally, Table 4 indicates that the each feature has a weight foreach state (zone). In fact, the weights can be zero for some zones orstates based on the current condition or strength of the Doppler and ECGsignals. For example, State 1 uses all four Doppler features and pRatio(ECG1). By contrast, State 0 (yellow) only looks at DF2 and pRatio. Insome embodiments, not every feature is used to determine the score. Instill other embodiments, the relative strength of a signal may be usedto adjust a weight. For example, a weak signal can be weighted less thana strong signal or have its weight decreased, while a strong signal canbe weighed more than a weak signal or have its weight increased. This isone example of adaptive weighting which allows the algorithm to adjustto the patient and/or changing conditions during use.

TABLE 4 Weights Feature>>>> Doppler 1 Doppler 2 Doppler 3 State (DF1)(DF2) (DF3) ECG 1 0 Wy1 Wy2 Wy3 Wye1 1 Wg1 Wg2 Wg3 Wge1 2 Wb1 Wb1 Wb3Wbe1 3 Wr1 Wr2 Wr3 Wre1

Table 5 illustrates an indicator score matrix for each of factors 1, 2,3, and 4. In general, the factor score represents the weightedlikelihood of the device being in any of states 0, 1, 2, and 3.

In general, the factor score is equal to the sum of the respectiveweights shown in Table 4 multiplied by the respective membershipfunction shown in Table 3 for each of states 0, 1, 2, and 3. As thedevice is expected to be in one of the states, the sum of all theweights in each class is equal to 1. The summation function is shown aselement 141 in FIG. 16.

TABLE 5 Indicator Score Score Factor 1 Factor 2 Factor 3 Factor 4 S0Wy1*PZ0D1 Wy2*PZ0D2 Wy3*PZ0D3 Wye1*PZ0E1 S1 Wg1*PZ1D1 Wg2*PZ1D2Wg3*PZ1D3 Wge1*PZ1E1 S2 Wb1*PZ2D1 Wb1*PZ2D2 Wb3*PZ2D3 Wbe1*PZ2E1 S3Wr1*PZ3D1 Wr2*PZ3D2 Wr3*PZ3D3 Wre1*PZ3E1

Table 6 illustrates the calculation of a probability or membership scorefor each of the parameters in the different states. Referring to FIG.16, the processor calculates a score 142 as described. The final scoreof each “class” is a weighted sum of the output scores from all theparameter membership functions (i.e. membership functions for DF1, DF2,DF3, and E1).

The weighted sum of the output scores from all the feature membershipfunctions for one class is as follows.

$S_{R} = {\sum\limits_{n}{{w_{R}(n)} \cdot {S_{R}(n)}}}$

The above equation represents one of the output scores for red (state 3in Table 2). “n” refers to the number of parameter features. Generally,the scores for each of the classes corresponding to the different statesincrease and decrease in likelihood with the membership function.

TABLE 6 Score Calculation S = Factor 1 + Factor 2 + Factor 3 + Factor 4

As shown in FIG. 16, final scores 142 are output by the processor 140.The processor then determines the state of navigation based on thehighest score. In other words, the highest score corresponds to thehighest likelihood, and the device is determined to be in the mostlikely location determined by the processor. In the above example, if SRis the highest score, the processor outputs a result related to State 3.In another example, if the highest score corresponds to state 0, theprocessor provides an output to the output device to display a yellowarrow.

The exemplary system includes exceptions to the above processing output.The exceptions may be based on expert knowledge, thresholds, or thelike. In various embodiments, the system includes two exceptions to theresults from above, which can be handled using a fuzzy logic basedalgorithm. The two exemplary exceptions include:

IF there are a number of consecutive heart beats in State 0 (Yellow),and the State 2 score (Blue Bull's Eye) is greater than State 1 andState 3 scores, then output “State 2”.

IF detect atrial fibrillation, or other ECG abnormalities (e.g. if ECG PWaves becomes bi-phasic), then default to State 3.

IF detect dominant retrograde flow, then default to State 3.

The selection of parameters and weighting play a significant role in theaccurate positioning and guidance of the system of the invention. Anexemplary device configured similar to the above has been found to havea high, clinically-acceptable level of accuracy with respect topositioning and location confirmation. The catheter tip was located atthe cavial atrial junction with repeated accuracy without the need forX-ray guidance.

Moreover, acquisition, conversion, processing and correlation steps,components, and capabilities may be included in the system 100 as neededdepending upon the type and number of sensors employed on theendovascular device 150.

Intravascular Placement and Positioning

Turning to FIGS. 17-19, the method of using a system in accordance withthe invention will now be described. The exemplary system is configuredsimilarly to FIG. 1. As discussed above, the methods for intravascularguidance and placement of endovascular devices disclosed herein aregenerally based on the recognition of patterns in the signals fordifferent physiological parameters and correlation of those signalpatterns.

Various aspects of invention relate to a method to substantiallyincrease the accuracy and reduce the need for imaging related to placingan intravascular catheter or other devices. The method generally relatesto the guidance, positioning, and placement confirmation ofintravascular devices such as catheters, stylets, guidewires and otherelongate bodies that are typically inserted percutaneously into thevenous or arterial vasculature, including flexible elongate bodies.

According to one embodiment of the present invention, there is provideda method for positioning an instrument in the vasculature of a bodyusing the instrument to determine a location to secure a device withinthe vasculature of a body; and securing the device to the body tomaintain the device in the location determined by the instrument. Afterthe passage of some period of time (as is common with patients who wearcatheters for an extended period of time), the instrument may be used tocalculate the current position of the device. Next, using the knownoriginal position and the now determined current position, the systemcan determine if the device has moved from the original position.

FIG. 17 illustrates an exemplary method 300 of catheter placement. Thisexample is for illustration purposes only. Similar conventionalcatheter, guide wire, or device introduction procedures may be tailoredfor the requirements of other therapeutic devices such as, for example,placement of hemodialysis catheters as well and placement of laser, RF,and other catheters for percutaneous treatment of varicose veins.

From top to bottom, FIG. 17 represents a single analysis or processingcycle. The cycle is repeated for each newly-acquired sample signal data.In general, the exemplary cycle is performed over and over until adesired destination is achieved.

In this example, the method 300 describes how a user would place a PICCcatheter using a guided vascular device with guidance informationdisplayed on an output device similar to that described above. Theexemplary catheter is similar in many respects to the device 150described above and includes one or more sensors. The output device 130indicates a navigation direction or position of the device based on thecollection, processing, and use of information related to the signaldata collected by the exemplary device.

In general, the exemplary system operates by collecting and manipulatinga reflected ultrasound signal to determine a position of the device. Inan exemplary embodiment, the desired destination of the device is wheretwo or more vessels join. However, one will appreciate that this methodmay be practiced in any of a wide variety of vascular junctions andother locations in both the venous and arterial vasculature. Otherexemplary positions where two or more vessels join include the junctionbetween a superior vena cava and an inferior vena cava and a junctionbetween an inferior vena cava and a renal vein.

While the techniques described herein may be practiced in a number ofclinical settings, the placement method 300 will be described inrelation to bedside catheter placement. The workflow presented incatheter placement method 300 begins with preparing the device forplacement. A user prepares the device in a conventional manner and asdescribed in greater detail above.

The medical professional next inserts the catheter into the vessel atstep 1700. This step is similar to the catheter introduction currentlyperformed by medical professionals. One exemplary insertion point is thebasilic vein 6 as shown in FIG. 19.

At step 1700, the user holds the devices in position in the vessel untilthe output device provides an indication of positive placement. Asdescribed above, the indication may be a change from a blinking greenlight to a solid green light. In the exemplary case of navigating thevenous vasculature, the output indicator provides a clear indication tothe user that the device is positioned in a vein.

Once in position in the vessel, the user holds the device in position orslowly moves the device forward for a few seconds. This step ensuresthat the signal processing algorithm can calibrate the data acquisitionand pattern recognition to the current patient data. Additionally, theprocessing system will analyze the sensor date to confirm that thesensor is placed in a vein not an artery. If the guidance systemincludes other optional signal acquisition and evaluation, such as useof an ECG signal as described below, this may also be an appropriatetime to establish and record a baseline. In some embodiments, theprocessing system can record the external ECG during the baseline. The Pwave magnitude can be extracted and the external P wave magnitude can beused in the pRatio to determine if the catheter tip is at the CAJ atevery time step. The processing system can also record information aboutthe patient (age, gender, heart conditions, etc) to further tune andcustomize the algorithm more to the patient.

After receiving confirmation from the system that the sensor/catheterhas been introduced into a vein, the clinician may start advancing thecatheter. The clinician navigates and positions the device as describedabove, for example, in relation to FIG. 19. The underlying operation ofthe guidance system is described in greater detail above.

Turning to step 1710, the device is enabled to transmit and receivesignals to collect information for use in the navigation and placementprocess of the invention. In various embodiments, the device transmits anon-imaging ultrasound signal into the vasculature using a non-imagingultrasound transducer on the endovascular device. The device receives areflected ultrasound signal with the non-imaging ultrasound transducer.One will appreciate that other signals may also be provided with theaddition of sensors and other mechanisms in accordance with theinvention.

At Step 1720, the system pre-processes the reflected ultrasound signalreceived by the non-imaging ultrasound transducer and the optionaladditional sensors. The pre-processing technique is described in greaterdetail above with respect to FIGS. 9 to 16. In general, thepre-processing involves data acquisition from the sensors and extractingof designated information parameters. In some respects, the extractedinformation represents the real-time sensor environment.

The method of using the exemplary device may optionally include aconfirmation subroutine to verify the location of the device. Althoughthe method described above involves reliable placement of the device inthe vasculature, for various reasons a user may wish to use additionaltechniques to further increase the reliability and accuracy of themethod.

Accordingly, at optional Step 1725, the system includes additionalnon-Doppler sensors for providing a confirmation signal as an input tothe pre-processor. The confirmation signal may be derived from a naturalsource or an artificial source. Because the system does not use theseother sources as the primary location information, the natural andartificial sources may be normal (regular) or irregular. Examples ofnatural and artificial sources, both regular and irregular, are shown inFIG. 18, and include a regular, natural source from the body 1726, airregular natural source from the body 1727, a regular artificial sourceapplied to the body 1728, and an irregular artificial source applied tothe body 1729.

A natural source is a source that naturally occurs within the body or isnaturally generated by the body. A normal or regular natural sourceincludes sinus ECG, RS amplitude, EEG, EMG, a gastric rumble, and flowacoustics in an open vessel or lumen including flow signatures forspecific vessel, junctions of vessels, organs or limbs. An irregularnatural source includes arrhythmia, abnormal EEG that can be noisy,abnormal EMG that can be noisy, and flow acoustics for blocked, occludedor partial flow through a vessel.

An artificial source is a source that artificial and not naturallyoccurring in the body or is something imposed onto the body. Anartificial source can be introduced to the body by localizedintroduction of a marker or indicia that can be detected by thenavigation system and used for confirmation. The artificial source mayaugment or interact with a system of the body or it may be used toprovoke a response from the body. Confirmation can be provided throughthe use of the marker or indicia itself, the response of the body to themarker or indicia or combinations thereof.

One will appreciate from the description herein how to incorporate anumber of conventional placement verification techniques in conjunctionwith the present method. In one example, a medical professional willapproximate a necessary length of catheter prior to the procedure. Inuse, the professional can verify that the amount of length that has beeninserted reasonably corresponds to what is expected for the positionindicated by the output device. In this manner, conventional,non-electronic positioning techniques can be used to verify properworking of the guidance system.

The method may also make use of other confirmatory techniques as wouldbe appreciated by one of skill in the art from the description herein.For example, the method may make use of confirmatory signals describedabove and illustrated in FIG. 18.

In step 1730, the pre-processed signal information is provided as inputsto a processor that implements artificial intelligence. As will beunderstood from the description herein, the pre-processing of the signalinformation plays an important role in the function of the processor andthe ultimate results of the system provided to the user.

In general, the pre-processor processes the signal data and outputsparameter information. The processor than uses the pre-processor outputsto make a determination and provide a result. For example, thepre-processor may receive streams of raw Doppler data and outputcorresponding total power values, ratios of antegrade/retrograde flow,and ratios of low velocity power to high velocity power. The processorthen uses the outputs to make a determination with respect to thesensor(s), for example, that the sensor is moving in a direction withthe blood flow or that the sensor is located in a particular position.Accordingly, the pre-processing and processing are interrelated toprovide accurate results to the clinician. The operation of theprocessor of the invention in conjunction with the pre-processor will bedescribed in more detail above with respect to FIGS. 9 to 16.

In various embodiments, the processor makes use of the parameterinformation by recognizing flow patterns and/or signatures in the flow.In various embodiments, the processor compares a respective processorinput to another input or to a calculated value. In various embodiments,the processor compares a respective processor input to values in alook-up table. The use of a look-up table provides the advantage ofreducing the number and complexity of processing operations that must beperformed.

At step 1740, the processor provides an output to the output devicebased on the processor determination. The output displays an indicationto the user regarding movement or positioning of the sensor.

Next, at step 1750, the user reads the output device and stops advancingthe catheter if the output device indicates that the catheter is in thedesired destination. Otherwise, the user continues advancing thecatheter and the process continues.

In an exemplary embodiment, the guidance system is configured to guide acatheter to the superior vena cava (SVC). In the region near the entryto the SVC, the output device displays a red light if thecatheter/sensor is determined to be in the jugular or other vein insteadof the SVC. In FIG. 19, this position is labeled “Red” and the catheteris shown in the internal jugular vein. In this situation the bloodstream flowing towards the heart comes towards the device. The systemmay also be configured to determine the proximity of the catheter/sensorto a structure. For example, if the catheter is facing a vessel wall andcannot be advanced, the output device displays a yellow light (marked“yellow” in FIG. 19). Further, the exemplary output device displays ablue light to indicate that the desired destination has been reached.

The method includes an optional Step 1760. The exemplary system isconfigured to determine a recommended direction of movement to reach thedesired destination and indicate the direction via the output device. Invarious embodiments, the system uses the historical positioninformation, present information, and/or other information to determinea recommended direction. In turn, the output device may include asymbol, color, graphic or other indicator to convey the recommendationto the user in Step 1760.

It should be understood that various alternatives to the embodiments ofthe invention described herein may be employed in practicing theinvention. For example if the target device position where in the brainfor example, then the processing algorithms and outputs could be changedto indicate that movement into the jugular is the correct direction(green indicator) and that movement towards the heart would be anincorrect direction (red indicator). The system indications andparameters can be altered depending upon the location of and accessroute taken to various different target sites in the vasculature.

The method of positioning an endovascular device in the vasculature of abody may also include additional or modified steps according to thespecific application or process being performed. Numerous additionalalternative steps are possible and may be used in a number ofcombinations to achieve the guidance and positioning results describedherein. Additional steps may include verifying that the length of theendovascular device inserted into the body is equivalent to theestimated device length prior to the procedure and/or inputting into thesystem the length of the endovascular device inserted in the body.

The method of positioning may also make use of various non-Dopplersignals for selective acquisition and processing. FIG. 22 illustrateshow the endovascular electrical signal can be use to trigger and gatethe processing of the ultrasound signals. The electrical signal acquiredfrom the endovascular sensor is periodic and related to the heart cycle(10 a). It is similar in shape with a known diagnostic ECG signal. Byanalyzing the waveforms, e.g., P-wave, QRS complex and the T-wave, anumber of events and time segments can be defined in the heart cycle.The P-wave event occurs when the P-wave amplitude is at its peak.The-R-wave event occurs when the R-wave amplitude is at its peak. Otherevents can be defined, e.g., when the R-wave amplitude is one thirdlower than the peak. Between such events time intervals can be defined.T1 is the time interval between 2 consecutive P-waves and indicates theheart rate. T2 is the time interval between two R-waves and similarlyindicates the heart rate. T3 is the time interval between the P and theR waves. T4 is the time interval between the R-wave and the subsequentP-wave. Other time intervals can be defined, as well. These intervalscan be defined in reference to a peak value of a wave, the beginning orend of such a wave, or any other relevant change in the electric signal.The events defined in a heart cycle can be used to trigger selectiveacquisition and/or processing of physiological parameters through thedifferent sensors, e.g., blood flow velocity information through theDoppler sensor. The time intervals can be used to gate the acquisitionand processing of physiological parameters like blood velocity, e.g.,only in the systole or only in the diastole. Thus more accurate resultscan be provided for guiding using physiological parameters. Graphs 10 band 10 c illustrate exemplary ultrasound data triggered on the T3interval.

One will appreciate that other triggers may be used. For example,variations in blood flow as identified by the Doppler signal can be usedto trigger and gate signal acquisition and processing based on therespiratory activity of the patient. The flow patterns as indicated bythe Doppler power spectrum change with the patient's respirations.Certain cardiac conditions like regurgitation also cause changes in theflow patterns with respiration. Such changes with respirations can beidentified, in particular when the strength of a certain pattern changeswith respirations. These identified changes can then be used to triggerand gate the acquisition and processing of physiological parametersrelative to the respiratory activity of the patient. Thus more accurateresults can be provided for guiding using physiological parameters.

Other features of the ECG waveform may also be used to trigger signalacquisition. For example, the relative changes in the QRS complex can beused to identify proximity of the sinoatrial node even in patients withatrial fibrillation, i.e., patients without a significant P-wavedetected by diagnostic ECG. In patients with atrial fibrillation, theP-wave cannot be typically seen with current diagnostic ECG systems.However, changes (i.e., significant increases in the QRS complexamplitude as identified by an endovascular sensor) may be indicative ofthe proximity of the sino-atrial node. In addition, an endovasculardevice can measure electrical activity which is not detected by astandard ECG system (e.g. the atrial electrical activity in a patientthought to have atrial fibrillation). Such changes in the waveform ofthe endovascular electrical signal can be used to position the sensorand the associated endovascular device at desired distances with respectto the sino-atrial node including in the lower third of the superiorvena cava or in the right atrium.

The methods, devices, and systems of the invention provide manyadvantages over conventional guidance and positioning systems andtechniques. One benefit of the new apparatus and method introducedherein is that it increases the probability of correct placement of anendovascular device in a placement procedure performed at the bedside.Moreover, because of the accuracy and redundancy of the positioningmethods described herein, it is believed that the use of the inventivemethods, devices, and systems will allow for endovascular deviceplacement without the need for imaging guidance, in particular withoutX-ray imaging and/or imaging for confirmation of placement and lack ofdevice migration. Another benefit of the new apparatus and method may beit provides for correct placement of an endovascular device in aplacement procedure on a larger group of patient's such as thoseexperiencing an aneurysm. Yet another benefit of the new apparatus andmethod introduced herein may be that it allows the detection of bloodclots in the vasculature or in catheters such as identifying the causefor a mal-functioning catheter, e.g., a central line.

Yet another benefit is related to the fact that the guided vascularaccess devices and the systems described herein may be inserted into theexisting healthcare workflow for placing endovascular devices into thevasculature. More specifically, embodiments of the invention provide newsensor-based endovascular devices, systems, and methods forintravascular guidance and placement of, for example, sensor-basedcatheters and/or guide wires. The properly-positioned, sensor-basedendovascular device is then used to guide the deployment of otherendovascular devices or facilitate the performance of other diagnosticor therapeutic procedures in the body such as, for example: (a) locationof heart valves for replacement heart valve procedures; (b)identification of the renal veins for therapy in those veins or in thekidneys; (c) identification of renal veins and/or the inferior vena cavafor IVC filter placement; (d) location of coronary sinus for placementof pacing leads or mitral valve modification devices; and (e) locationof pulmonary veins for sensor placement and/or performance of therapysuch as ablation treatment for atrial fibrillation. A wide variety ofother diagnostic or therapeutic procedures may also benefit from theplacement of device or performance of therapy at specific locations inthe vasculature identified by the sensor correlation techniquesdescribed herein.

In some embodiments, the systems and methods of embodiments of theinventive guidance system described herein are utilized to locate, guideand position catheters and/or guide wires equipped with sensorsdescribed herein within the vessels of the venous system. Theembodiments described herein may also be utilized in the vessels of thearterial system as well. In one aspect, the guided vascular accessdevices described herein may be used for the guidance, positioning, andplacement confirmation of intravascular catheters used in a wide numberof clinical applications. Exemplary clinical applications that wouldbenefit from embodiments of the invention include the placement of, forexample, central venous access catheters (PICC), hemodialysis cathetersand the placement of catheters, positioning of endovascular devices inthe vasculature of the brain for treatment of stroke, placement of leadsor other brain based therapy or therapy devices or treatment systems forpercutaneous treatment of varicose veins. Moreover, particular musclesor muscle groups may be selected for EMG stimulation and/or sensorcollection in support of one of more methods and devices describedherein where the EMG signals are used to confirm and/or correlate aposition in the vasculature. This aspect may be particularly helpfulwhen identifying portions of the vasculature in the legs forlocalization of varicose veins, localization of the femoral veins orpositioning of a vessel harvesting device within the great saphenousvein, for example.

Other System Features

In various embodiments, all or some of the operations of the abovemethod are automated. In various embodiments, the system is remotelycontrolled, networked, or transfers information through a wirelessinterface. Such information can be coordinated with a central locationvia, for example, a wireless network.

In many clinical applications, endovascular devices are required to havethe device tip (distal end) to be placed at a specified location in thevasculature. For example, CVC and PICC lines are required to have theirtip placed in the lower third of the superior vena cava. However, forexample, due to lack of a guidance system at the patient's bedside,users currently place the catheters into the patient's body blindly,often relying on x-ray to confirm the location of the catheter a coupleof hours after initial placement. Since the CVC or a PICC line can bereleased for use only after tip location confirmation, the patienttreatment is delayed until after X-ray confirmation has been obtained.Ideally, users should be able to place the catheter at the desiredlocation with high certainty and with immediate confirmation of tiplocation. Building a user-friendly, easy-to-use system which integrateselectrical activity information with other types of guiding information,devices and techniques described herein.

While the simplified user interface provides a clear indication to aclinician the position and direction of the distal end of the device, itmay be desirable to store the guidance information during the procedure.The position information, and in particular the processor results, canbe digitally recorded so that it can be used to print a report for thepatient's chart. Storing of patient information, exporting the data to astandard medium like a memory stick, and printing this information to aregular printer may be especially useful when the device and systemdisclosed in the current invention are used without chest X-rayconfirmation to document placement at the cavo-atrial junction of theendovascular device.

In some embodiments, with respect to the descriptions and figuresprovided herein, such as FIGS. 9-18 which disclose manipulating acousticand electrical signals during preprocessing and processing steps, acomputer readable storage medium having embodied thereon a program canbe used with the devices, systems and methods disclosed herein. Theprogram can be executed by a processor to perform a method forpositioning an endovascular instrument in a vasculature, the methodcomprising manipulating a reflected acoustic signal from a sensor on theinstrument positioned within a blood vessel to extract one or moreacoustic features from the acoustic signal; manipulating an electricalsignal from a lead on the instrument positioned within a blood vessel toextract one or more electrical features from the electrical signal;generating an output related to guidance or a position of the instrumentwithin the blood vessel using a computer readable set of rules toevaluate the one or more extracted features; and displaying one of apredetermined number of indications of guidance or positioncorresponding to the output.

In some embodiments, the computer readable set of rules on the computerreadable medium comprises one or more predefined membership functionsthat indicate one or more positional states of the instrument. Thecomputer readable storage medium further comprises instructions forinputting the extracted features into the one or more predefinedmembership functions and for generating one or more scores that indicatethe likelihood of membership in one or more positional states. Thecomputer readable storage medium can further comprise instructions forweighting the extracted features or one or more membership functionsbefore generating one or more scores, wherein weighting the extractedfeatures or one or more membership functions comprises applyingweighting factors to the extracted features or one or more membershipfunctions, wherein the weighting factors apply less weight to anextracted feature or one more membership function based on a weakacoustic or electrical signal, wherein the weighting factors apply moreweight to an extracted feature or one more membership function based ona strong acoustic or electrical signal.

In some embodiments, extracted acoustic features used by the programrelate to, for example, the direction of movement of the instrumentrelative to flow in the vasculature, the overall flow energy in thevasculature measured by the sensor, the overall flow velocity in thevasculature measured by the sensor, a ratio of a low frequency flowpower to a high frequency flow power, an acoustic signal obtained duringa portion of a heartbeat, the portion of a heart beat during theoccurrence of retrograde flow produced by atrial contraction, theportion of a heart beat during the occurrence of retrograde flow at theend of systole, and/or the portion of a heart beat during the occurrenceof antegrade flow during diastole.

In some embodiments, extracted electrical features used by the programrelate to, for example, a portion of an QRS complex, a ratio of amagnitude of a P-wave measured by the sensing electrode and a magnitudeof a P-wave measured by an external electrode, and/or an indication ofthe presence of a biphasic P-wave.

The foregoing descriptions of specific embodiments of the presentinvention have been presented for purposes of illustration anddescription. They are not intended to be exhaustive or to limit theinvention to the precise forms disclosed, and obviously manymodifications and variations are possible in light of the aboveteaching. The embodiments were chosen and described in order to bestexplain the principles of the invention and its practical application,to thereby enable others skilled in the art to best utilize theinvention and various embodiments with various modifications as aresuited to the particular use contemplated. It is intended that the scopeof the invention be defined by the Claims appended hereto and theirequivalents.

1. A positioning system, comprising: a transducer for mounting on adistal end of an endovascular instrument; a control system connected tothe transducer, the control system being configured to generate andreceive an acoustic signal using the transducer; a pre-processorreceiving the acoustic signal as an input, the pre-processor containingcomputer-readable instructions for manipulating the signal input toextract one or more acoustic features from the signal input; a processorconfigured to receive the one or more extracted features, the processorcontaining a computer-readable set of rules to evaluate the extractedfeatures using the rules to generate an output related to guidance ofthe instrument within a blood vessel or a position of the instrumentwithin the blood vessel; and an output device for displaying anindication of the output generated by the processor.
 2. The positioningsystem of claim 1, further comprising: a sensing electrode for mountingon the instrument, the sensing electrode being connected to the controlsystem; wherein the control system is further configured to receive anelectrical signal from the sensing electrode, and wherein thepre-processor further contains instructions for manipulating thereceived electrical signal to extract one or more features related tothe electrical signal; and wherein the computer-readable set of rulescontains a rule to evaluate the one or more electrical features.
 3. Thepositioning system of claim 1, wherein the acoustic signal comprises anon-imaging ultrasound signal.
 4. The positioning system of claim 2,wherein the processor evaluates the one or more electrical features toconfirm the output related to the guidance or a position of theinstrument within a blood vessel.
 5. The positioning system of claim 2,wherein the electrical signal comprises an ECG signal.
 6. Thepositioning system of claim 2, wherein the electrical signal comprisesan EMG signal.
 7. The positioning system of claim 2, wherein theelectrical signal comprises an EEG signal.
 8. The positioning system ofclaim 1, wherein the computer-readable set of rules contained in theprocessor includes artificial intelligence programming.
 9. Thepositioning system of claim 2, wherein the computer-readable set ofrules contained in the processor includes artificial intelligenceprogramming.
 10. The positioning system of claim 1, wherein thecomputer-readable set of rules contained in the processor evaluates theextracted features based on at least one of inference rules, an expertsystem, a neural network, and logic.
 11. The positioning system of claim2, wherein the computer-readable set of rules contained in the processorevaluates the extracted features based on at least one of inferencerules, an expert system, a neural network, and logic.
 12. Thepositioning system of claim 1, the computer-readable set of rulesfurther comprising: a rule to evaluate whether a power level of theacoustic signal is below a threshold.
 13. The positioning system ofclaim 2, the computer-readable set of rules further comprising: a ruleto evaluate whether a power level of the acoustic signal is below athreshold.
 14. The positioning system of claim 1, the computer-readableset of rules further comprising: a rule to evaluate whether an antegradeflow in the blood vessel is dominant over a retrograde flow in the bloodvessel.
 15. The positioning system of claim 2, the computer-readable setof rules further comprising: a rule to evaluate whether an antegradeflow in the blood vessel is dominant over a retrograde flow in the bloodvessel.
 16. The positioning system of claim 1, the computer-readable setof rules further comprising: a rule to evaluate whether a retrogradeflow in the blood vessel is dominant over an antegrade flow in the bloodvessel.
 17. The positioning system of claim 2, the computer-readable setof rules further comprising: a rule to evaluate whether a retrogradeflow in the blood vessel is dominant over an antegrade flow in the bloodvessel.
 18. The positioning system of claim 1, the computer-readable setof rules further comprising: a rule to evaluate whether a low frequencysignal dominates both an antegrade flow in the blood vessel and aretrograde flow in the blood vessel.
 19. The positioning system of claim2, the computer-readable set of rules further comprising: a rule toevaluate whether a low frequency signal dominates both an antegrade flowin the blood vessel and a retrograde flow in the blood vessel.
 20. Thepositioning system of claim 2, wherein the control system is configuredto synchronize the acoustic signal and the electrical signal.
 21. Thepositioning system of claim 2, the computer-readable set of rulesfurther comprising: a rule to evaluate a P-wave in the receivedelectrical signal relative to a reference.
 22. The positioning system ofclaim 21, the rule to evaluate a P-wave in the received electricalsignal relative to a reference further comprising: providing an outputwhen the P-wave in the received electrical signal is elevated above thereference.
 23. The positioning system of claim 21, the rule to evaluatea P-wave in the received electrical signal relative to a referencefurther comprising: providing an output when the P-wave in the receivedelectrical signal is at or below the reference.
 24. The positioningsystem of claim 21, the rule to evaluate a P-wave in the receivedelectrical signal relative to a reference further comprising: providingan output when the P-wave in the received electrical signal is biphasic.25. The positioning system of claim 1, wherein the output related to theguidance or a position comprises one of a plurality of states, eachstate related to a predetermined set of conditions of instrumentmovement or position.
 26. The positioning system of claim 1, wherein theoutput related to the guidance or position comprises an indication ofthe most probable condition selected from the group consisting of:instrument moving in a desired direction, instrument moving in anundesired direction, and instrument positioned in a desired location.27. The positioning system of claim 2, wherein the output related to theguidance or position comprises an indication of the most probablecondition selected from the group consisting of: instrument moving in adesired direction, instrument moving in an undesired direction, andinstrument positioned in a desired location.
 28. The positioning systemof claim 27, wherein the indication of the instrument moving in adesired direction is different from the indication of the instrumentpositioned in a desired location.
 29. The positioning system of claim 2,wherein the one or more features related to the electrical signalcorresponds to a pre-selected portion of a regular electrical waveproduced by the body.
 30. The positioning system of claim 29 wherein theelectrical wave is an electrocardiogram and the pre-selected portion isan RS amplitude.
 31. The positioning system of claim 29 wherein theelectrical wave is an electrocardiogram and the pre-selected portion isan electrocardiogram segment.
 32. The positioning system of claim 29wherein the electrical wave is an electrocardiogram and the pre-selectedportion is an electrocardiogram interval.
 33. The positioning system ofclaim 2, wherein the one or more features related to the electricalsignal corresponds to a pre-selected portion of an irregular electricalwave produced by the body.
 34. The positioning system of claim 33,wherein the one or more features related to the electrical signalcorrespond to a pre-selected portion of an electrical wave produced by abody having arrhythmia.
 35. The positioning system of claim 5, whereinthe one or more acoustic features corresponds to a ratio of a retrogradepower of the flow in the blood vessel to an antegrade power of the flowin the blood vessel during a single ECG cycle.
 36. The positioningsystem of claim 1, wherein the one or more acoustic features correspondsto a ratio of a low frequency flow power to a high frequency flow power.37. The positioning system of claim 1, wherein the at least one acousticfeature corresponds to an acoustic signal obtained during a portion of aheart beat.
 38. The positioning system of claim 37, wherein the at leastone acoustic feature corresponds to the portion of a heart beat duringthe occurrence of retrograde flow produced by atrial contraction. 39.The positioning system of claim 37, wherein the at least one acousticfeature corresponds to the portion of a heart beat during the occurrenceof antegrade flow during systole.
 40. The positioning system of claim39, wherein the at least one acoustic feature corresponds to the portionof a heart beat during the occurrence of retrograde flow at the end ofsystole.
 41. The positioning system of claim 37, wherein the at leastone acoustic feature corresponds to the portion of a heart beat duringthe occurrence of antegrade flow during diastole.
 42. The positioningsystem of claim 2, wherein the one or more features related to theelectrical signal corresponds to a portion of an QRS complex.
 43. Thepositioning system of claim 2, wherein the one or more features relatedto the electrical signal corresponds to a ratio of a magnitude of aP-wave measured by the sensing electrode and a magnitude of a P-wavemeasured by an external electrode.
 44. The positioning system of claim2, wherein the one or more features related to the electrical signalcorresponds to an indication of the presence of a biphasic P-wave.
 45. Amethod of positioning an endovascular instrument in a vasculaturecomprising: inserting a system including an endovascular device and atleast one transducer into the lumen of a patient; transmitting anacoustic signal within the lumen; pre-processing a reflected signal toextract one or more acoustic features; and processing the one or moreacoustic features using a computer readable set of rules to produce anoutput related to guidance of the instrument within a blood vessel or aposition of the instrument within the blood vessel.
 46. The method ofclaim 45, wherein the processing is performed based on a predefined setof inference rules related to one of a set of navigation states.
 47. Themethod of claim 45, wherein the processing is performed based on apredefined set of probabilities related to one of a set of navigationstates.
 48. The method of claim 45, wherein the processing is performedbased on a comparison of the one or more parameters to a predefined setof parameters in a database.
 49. The method of claim 45, furthercomprising displaying the output related to guidance of the devicewithin the blood vessel or a position of the instrument within the bloodvessel.
 50. The method of claim 49, wherein the output comprises anindication of the most probable condition selected from the groupconsisting of: instrument moving in a desired direction, instrumentmoving in an undesired direction, and instrument positioned in a desiredlocation.
 51. The method of claim 50 wherein the desired direction istowards the heart.
 52. The method of claim 50 wherein the undesireddirection is away from the heart.
 53. The method of claim 50 wherein thedesired direction is with a flow of blood returning to the heart. 54.The method of claim 50 wherein the undesired direction is against a flowof blood returning to the heart.
 55. The method of claim 50 wherein thedesired location is within a lower third of the superior vena cava. 56.The method of claim 50 wherein the desired location is proximate to thecaval atrial junction.
 57. The method of claim 50 wherein the desiredlocation is within the superior vena cava proximate to the caval atrialjunction.
 58. The method of claim 49, further comprising: manipulatingthe device in the blood vessel in response to the output.
 59. The methodof claim 58 the manipulating step further comprising: withdrawing theinstrument.
 60. The method of claim 58 the manipulating step furthercomprising: advancing the instrument.
 61. A computer readable storagemedium having embodied thereon a program, the program being executed bya processor to perform a method for positioning an endovascularinstrument in a vasculature, the method comprising: manipulating areflected acoustic signal from a sensor on the instrument positionedwithin a blood vessel to extract one or more acoustic features from theacoustic signal; manipulating an electrical signal from a lead on theinstrument positioned within a blood vessel to extract one or moreelectrical features from the electrical signal; generating an outputrelated to guidance or a position of the instrument within the bloodvessel using a computer readable set of rules to evaluate the one ormore extracted features; and displaying one of a predetermined number ofindications of guidance or position corresponding to the output.
 62. Thecomputer readable storage medium of claim 61, wherein the computerreadable set of rules to evaluate the one or more extracted featurescomprises one or more predefined membership functions that indicate oneor more positional states of the instrument.
 63. The computer readablestorage medium of claim 62, further comprising inputting the extractedfeatures into the one or more predefined membership functions and forgenerating one or more scores that indicate the likelihood of membershipin one or more positional states.
 64. The computer readable storagemedium of claim 63, further comprising weighting the extracted featuresor one or more membership functions before generating one or morescores.
 65. The computer readable storage medium of claim 64, whereinweighting the extracted features or one or more membership functionscomprises applying weighting factors to the extracted features or one ormore membership functions, wherein the weighting factors apply lessweight to an extracted feature or one more membership function based ona weak acoustic or electrical signal, wherein the weighting factorsapply more weight to an extracted feature or one more membershipfunction based on a strong acoustic or electrical signal.
 66. Thecomputer readable storage medium of claim 64, further comprisingselecting the highest score and determining the positional state basedon the highest score.
 67. The computer readable storage medium of claim64 wherein one score of the one or more scores relates extractedacoustic features to the direction of movement of the instrumentrelative to flow in the vasculature.
 68. The computer readable storagemedium of claim 64 wherein one score of the one or more scores relatesacoustic features to the overall flow energy in the vasculature measuredby the sensor.
 69. The computer readable storage medium of claim 64wherein one score of the one or more scores relates acoustic features tothe overall flow velocity in the vasculature measured by the sensor. 70.The computer readable storage medium of claim 61, wherein the one ormore acoustic features corresponds to a ratio of a low frequency flowpower to a high frequency flow power.
 71. The computer readable storagemedium of claim 61, wherein the at least one acoustic featurecorresponds to an acoustic signal obtained during a portion of a heartbeat.
 72. The computer readable storage medium of claim 71, wherein theat least one acoustic feature corresponds to the portion of a heart beatduring the occurrence of retrograde flow produced by atrial contraction.73. The computer readable storage medium of claim 71, wherein the atleast one acoustic feature corresponds to the portion of a heart beatduring the occurrence of retrograde flow at the end of systole.
 74. Thecomputer readable storage medium of claim 71, wherein the at least oneacoustic feature corresponds to the portion of a heart beat during theoccurrence of antegrade flow during diastole.
 75. The computer readablestorage medium of claim 61, wherein the one or more electrical featurescorresponds to a portion of an QRS complex.
 76. The computer readablestorage medium of claim 61, wherein the one or more electrical featurescorresponds to a ratio of a magnitude of a P-wave measured by thesensing electrode and a magnitude of a P-wave measured by an externalelectrode.
 77. The computer readable storage medium of claim 61, whereinthe one or more electrical features corresponds to an indication of thepresence of a biphasic P-wave.
 78. A method of determining a position ofa medical device in the vasculature of a patient, comprising:transmitting a signal in the vasculature comprising an ultrasound signalfrom a distal end of a device; receiving a reflected ultrasound signal;extracting an ultrasound feature from the reflected ultrasound signal;receiving an electrical signal from a lead on the device; extracting anECG feature from the received electrical signal; calculating a pluralityof indicator scores using the extracted features; and identifying apositional state by comparing the indicator scores.
 79. The method ofclaim 78, wherein each feature infers a distinct position in thevasculature.
 80. The method of claim 78, the calculating step furthercomprising: inputting the extracted features into a plurality ofindicator equations representing positioning probabilities.
 81. Themethod of claim 80, wherein the indicator equations correspond tomembership functions.
 82. The method of claim 80, the indicatorequations further comprising: applying a weighting factor related to theextracted feature used in the indicator equation.
 83. The method ofclaim 78, the identifying step further comprising: selecting thepositional state that corresponds to the highest indicator score. 84.The method of claim 78 the calculating step further comprising: solvingpreset equations based on a correlation between an extracted feature anda probability of a particular position or state of navigation of thedevice.
 85. The method of claim 78 wherein one indicator score in theplurality of indicator scores relates extracted acoustic features to thedirection of movement of the device relative to flow in the vasculature.86. The method of claim 78 wherein one indicator score in the pluralityof indicator scores relates acoustic features to the overall flow energyin the vasculature measured by the sensor.
 87. The method of claim 78wherein one indicator score in the plurality of indicator scores relatesacoustic features to the overall flow velocity in the vasculaturemeasured by the sensor.